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Comparison table of CD family of immunocyte surface antigen molecules (CD1-CD247)

Background

CD: cluster designation of monoclonal antibodies (clusters of differentiation)
Designated at the 1st to 7th Workshops on International Human Leukocyte Differentiation Antigens
The last conference was in 2000.  The next conference is in 2004.
HLDA Workshops are the primary mechanism to characterize leukocyte surface antigenic molecules and epies; erythroid antigens are now included 
For 1st to 6th workshops, antibodies were submitted to the organizing laboratory, coded and sent to participating laboratories for testing against various cell types.  For the 7th workshop, a CD designation could be established for a molecule if its gene has been cloned and at least one specific monoclonal antibody had been studied in the Workshop
Interpretation should be based on cellular distribution of staining, proportion of positively stained cells, staining intensity and cutoff levels.
 

CD1

Family of non-polymorphic MHC class I-like glycoproteins
Also member of immunoglobulin superfamily
On chromosome 1q22-23 (not MHC linked)
Has 5 different subsets, all noncovalently associated with 12 kd beta 2 microglobulin
Function: restrict T cell responses to certain antigens; may mediate thymic T cell development
Positive staining (normal): cortical thymocytes (70%), activated T cells, Langerhans cells, interdigitating dendritic cells
Positive staining (disease): pre T ALL with cortical thymocyte phenotype; Langerhans cell histiocytosis
Negative staining: mature peripheral T cells

CD1a

Positive staining (normal): Dendritic cells in dermis/epidermis of benign inflammatory skin disorders
Positive staining (disease): Langerhans cell histiocytosis (fairly specific), myeloid leukemias, some B cell malignancies; dendritic cells in most peripheral cutaneous T cell lymphomas, AJCP 2001;116:72
Negative staining: normal B cells, most cutaneous peripheral B cell lymphomas (? reflects replacement of reactive pattern containing dendritic cells with a neoplastic pattern of B cells)
Micro images:  Langerhans cell histiocytosis
Micro images (AJSP subscribers): pulmonary Langerhans cell histiocytosis
Micro images (Hum Path subscribers): Langerhans cell histiocytosis
References:  AJSP 2001;25:630
 

CD1b


Positive staining (disease): myeloid leukemias and some B cell malignancies
Negative staining: normal B cells
 

CD1c



Positive staining (normal): subset of normal peripheral B cells
Positive staining (disease): myeloid leukemias and some B cell malignancies
Negative staining: normal B cells
 

CD1d

Positive staining (normal): thymus (low levels), bowel
 

CD1e
 

CD2



Aka E rosette receptor, LFA-2 (leukocyte function antigen)
Function: binds CD58 / LFA-3 on antigen-presenting cells, and induces costimulatory signals in T cells
Also regulates T and NK-mediated cytolysis, inhibits apoptosis of activated peripheral T cells, mediates T cell cytokine production, regulates T cell anergy
Positive staining (normal): thymocytes (95%), mature peripheral T cells (almost all), NK cells (80-90%), thymic B cells (50%)
Micro images: extranodal NK/T cell lymphoma, nasal type
 

CD2R

CD2 epies restricted to activated T cells
Positive staining: activated T cells, ? NK cells
 

CD3



Aka OKT3
Function: complex (5 chains) of integral membrane glycoproteins assembled as a complex; has long cylasmic tail with antigen recognition activation motif; complex is then down regulated
Also subdivided into delta, epsilon, gamma subtypes
Cylasmic expression at early T cell differentiation, then membranous expression
Most specific T cell antibody
Positive staining (normal): thymocytes, peripheral T cells, NK cells; also Purkinje cells of cerebellum
Positive staining (disease): 80% of T cell lymphomas
Negative staining: gamma delta T cell receptors, most B cell lymphomas
Micro images: CD3 epsilon-testicular NK/T cell lymphoma (figure 3D)
Micro images (AJSP subscribers): achalasia, post-transplant lymphoproliferative disease in liver
References: AJSP 2001;25:1413
 

CD4



Aka OKT4, T helper/inducer
On chromosome #12p
Nonpolymorphous glycoproteins belonging to immunoglobulin superfamily
Serves as HIV receptor on T cells (as do chemokine receptors CCR5 and CXCR4), macrophages, brain
CD4+ T cells are killed by HIV
Coreceptor in MHC class II-restricted antigen induced T cell activation
Binds to nonpolymorphic region of class I molecules; may increase avidity of cell-cell interactions
Positive staining (normal): thymocytes (80-90%), mature T cells (65%, T helper and CD4/CD8+ thymocytes), macrophages, Langerhans cells, dendritic cells, granulocytes
Positive staining (disease): pityriasis lichenoides
Micro images: acute demyelinating disease, extranodal NK/T cell lymphoma, nasal type
 

CD5



Belongs to ancient scavenger receptor family
Is physically and functionally coupled with T cell receptor-zeta-CD3 signal transducer complex
CD5+ B cells produce “generalist antibodies” - polyreactive low affinity "natural" antibodies to exogenous antigens (tetanus toxoid, lipopolysaccharide) as well as autoreactive antibodies (ssDNA, thyroglobulin, insulin)
   Note: sharks only have polyreactive IgM
   Note: monoreactive IgG is produced by  < 0.1% of circulating B cells, from positive selection and somatic
   point mutation
First line of defense against antigens; have a low activation threshold; are the only line of defense for those who cannot produce specific antibody
Produce antibodies using germ line (non mutated) configuration of gene segments, usually IgM
Production elevated in rheumatoid arthritis (27-52% of circulating B cells vs. 20% normal)
CD5 may serve as a dual receptor, giving either stimulatory or inhibitory signals depending both on the cell type and the development stage

Positive staining (normal): B cells of mantle zone of spleen and lymph nodes; B cells in peritoneal and pleural cavities; almost all T cells;

In fetus, most B cells in spleen and cord blood are CD5 positive

Positive staining (disease): B cell CLL/SLL, mantle cell lymphoma, most T malignancies, thymic carcinomas (70%)

Negative staining: spindle cell thymomas, MALT lymphoma, follicular lymphoma
Micro images: extranodal NK/T cell lymphoma, nasal type,  mantle cell lymphoma (figure 3D)
 

CD6



Adhesion molecule mediating the binding of developing thymocytes with thymic epithelial cells
May be involved in autoimmunity and graft vs. host disease (GVHD)
Antibodies to CD6 are used to deplete T cells from bone marrow transplants to prevent GVHD
Positive staining (normal): low levels on immature thymocytes, high levels on mature thymocytes
 

CD7



Membrane glycoprotein and Fc receptor for IgM
Homologous to TCR gamma, Ig kappa
Membrane expression early during T ontogeny, before TCR rearrangement, persists until terminal stages of T cell development
Lower expression in memory T cells vs. naive T cells

Positive staining (normal): mature peripheral T cells (85%), post-thymic T cells (majority), NK cells (majority), some myeloid cells

Positive staining (disease): T cell ALL; AML (especially M4/M5), chronic myelogenous leukemia, blasts in transient myeloproliferative disorder

Negative expression: B cell ALL, Sezary syndrome, adult T cell leukemia/lymphoma
Micro images: extranodal NK/T cell lymphoma, nasal type
 

CD8



Aka OKT8, T cell suppressor/cytotoxic cells
On chromosome #2
MHC class I restricted receptor; binds to nonpolymorphic region of class I molecules; may increase avidity of cell-cell interactions
Associated with lymphoepithelioma-like carcinoma of lung (AJSP 2002;26:715)

Positive staining (normal): T cells (25-35% of mature peripheral T cells, most cytotoxic T cells, CD4/CD8+ thymocytes); NK cells (30%-which are also CD3 negative); cortical thymocytes (70-80%), epidermotrophic lymphocytes in mycosis fungoides (AJSP 2002;26:450)

Micro images: lymphoepithelioma-like carcinoma of cervix-figure 3acute demyelinating disease

Micro images (Mod Path subscribers): nodal cytotoxic T cell lymphoma

Reference: Mod Path 2002;15:1131
 

CD9



May mediate platelet activation and aggregation
Antibodies are used to purge bone marrow prior to peripheral stem cell bone marrow transplant
Viral co-receptor
Positive staining (normal): pre B cells, B cell subset, T cells, macrophages, platelets, eosinophils, basophils, megakaryocytes, endothelial cells, brain, peripheral nerve, vascular smooth muscle, cardiac muscle, epithelia
 

CD10



Aka Common Acute Lymphoblastic Leukemia Antigen (CALLA), neutral endopeptidase 24.11, neprilysin, enkephalinase
Cell membrane metallopeptidase, characteristic marker of follicular center cells and follicular lymphoma, but also widely distributed in normal tissue and neoplasms; also localized to brush border in small bowel mucosa
Inactivates bioactive peptides
Uses:
Acute lymphoblastic leukemia: one of first markers to identify leukemic cells in children (hence its name)
Breast: marker of myoepithelial cells, Mod Path 2002;15:397
Burkitt lymphoma: confirm diagnosis
Colonic carcinogenesis: increase in stromal cells from mild to severe dysplasia to invasive carcinoma, Hum Path 2002;33:806-811
Endometriosis: helpful in identifying areas of endometriosis if sparse glandular tissue
Follicular lymphoma: to confirm diagnosis
Hepatocellular carcinoma vs. nonhepatocellular carcinomas: 68% sensitive and >95% specific with canalicular pattern, AJSP 2001;25:1297AJSP 2002;26:978, although another study recommends Hepatocyte, MOC31, and pCEA but not CD10, Mod Path 2002;15:1279
Microvillous inclusion disease: strong CD10+ cylasmic staining vs. linear brush border staining in normals, AJSP 2002;26:902
Positive staining (normal): adrenal cortex, pre-B cells, brain, choroid plexus, cortical thymocytes, endometrial stroma, follicular center cells, granulocytes, kidney microvilli, liver, lymphohemaoietic precursors, male GU epithelium, mesonephric remnants, myoepithelial cells (breast), neutrophils, ovary, placenta (cytotrophoblast, intermediate trophoblast, syncytiotrophoblast), small intestine (linear brush border staining)
Positive staining (disease): adenomyosis of endometrium, preB ALL (75%), CML in blast crisis (90%), colonic carcinoma, dermatofibroma, dermatofibrosarcoma, endometrial adenocarcinoma (may be present in desmoplastic stroma), endometrial stromal tumors, follicular center cell lymphomas, gastric carcinoma, glioma, hepatocellular carcinoma (canalicular pattern similar to polyclonal CEA), malignant mixed mullerian tumors, mediastinal germ cell tumors, melanomas, mesonephric tumors, microvillous inclusion disease (strong cylasmic staining), mullerian adenosarcoma, pancreatic adenocarcinoma, pancreatic solid-pseudopapillary tumor, placental site trophoblastic tumor, primary mediastinal B cell lymphomas (some), prostate carcinoma, renal cell carcinoma, renal cell sarcoma, rhabdomyosarcoma and other sarcomas, schwannoma, tumor of wolffian origin of broad ligament and ovary, urothelial carcinoma, uterine carcinoma, uterine cellular leiomyomas (50%), uterine leiomyosarcomas and other uterine sarcomas
Negative staining: myeloid and erythroid precursors, other female genital tract tumors (including clear cell carcinomas)
Micro images: follicular center cells (figure 1), intranodal heteroic mammary ducts (figure 1C),
Micro images (AJSP subscribers): endometrial stromal tumor #1 (negative), #2,  hepatocellular carcinoma#1, #2,   mesonephric carcinoma of uterus, mesonephric derivatives in men,   microvillous inclusion disease#1, #2 (controls),   vulvar, vaginal and cervical lesionsuterus and trophoblast,   fallopian tube and ovary
Micro images (Hum Path subscribers): canalicular pattern in hepatocellular carcinoma (figure C), gastric carcinoma at apical border (figure B),   colonic adenoma, colonic carcinoma#1, #2
Micro images (Mod Path subscribers): canalicular pattern in hepatocellular carcinoma (figure B), malignant mixed mullerian tumor#1, #2, #3breast myoepitheliumbreast adenosisbreast DCISinvasive ductal carcinoma of breastdiffuse large B cell lymphomaadenomyosis
References: AJSP 2002;26:978, AJSP 2001;25:1540, AJSP 2002;26:902, AJSP 2003;27:178, Mod Path 2002;15:1279, Mod Path 2002;15:923, Mod Path 2002;15:397, Mod Path 2002;15:413, Mod Path 2002;16:22
 

CD11



CD11a, b and c all have same beta chain (CD18)
Members of integrin receptor family; heterodimers of noncovalently associated alpha and beta subunits
 

CD11a



Aka alpha L; LFA-1 (in complex with CD18)
An alpha integrin chain that binds to CD18 and mediates leukocyte adhesion and lymphocyte recirculation through lymph nodes
With CD18, binds to ICAM-1 (CD54, leukocyte adhesion molecule) and ICAM-2 (CD102)
Facilitates lymphocyte blastogenesis, cellular cytotoxicity, lymphocyte-endothelial cell adhesion, and binding to unopsonized bacteria (E. coli) and fungi (Hislasma capsulatum)
Note: patients with leukocyte adhesion deficiency (mutations in CD18) have often fatal immunodeficiency early in life
Marker of differentiation in acute promyelocytic leukemia
Positive staining (normal): all leukocytes
Negative staining: platelets
 

CD11b



Aka CR3, iC3b receptor
Mediates phagocytosis of particles opsonized with iC3b
Facilitates neutrophil aggregation, adhesion to substrates by opsonization, chemotaxis
Ligands include fibrinogen, Factor X, ICAM-1, Saccharomyces cerevisiae, Staphylococcus epidermidis, Hislasma capsulatum,
Note: C3 is common to classical and alternate complement pathway, and serves as an amplification step
C3b (activated C3) can amplify by cleaving more C3 via the alternate complement pathway
Positive staining (normal): follicular dendritic cells, granulocytes, macrophages, myeloid cells beginning with promyelocytes, NK cells, some B/T cells
Positive staining (disease):  AML-M1-M3 (35-70%), M4-M5 (80-90%); hairy cell leukemia (virtually all)
 

CD11c



Aka CR4, iC3b receptor
Clears opsonized particles and immune complexes; also binds to fibrinogen and is involved in adhesion of monocytes and neutrophils to endothelium
Member of beta 2 family of integrin receptors
Prognostic value: associated with good prognosis in B-CLL
Positive staining (normal): 50% of activated CD4/CD8+ T cells; granulocytes, lymphocytes, macrophages, NK cells
Positive staining (disease): AML-M4-M5 (50%); hairy cell leukemia (virtually all), B-CLL
 

CD12



Positive staining (normal): granulocytes, monocytes, NK cells, platelets
Negative staining: basophils, bone marrow precursors, AML
 

CD13



Aka AminoPeptidase N, APN
Myeloid antigen, although CD33 is more specific
Peptide cleaving enzyme of brush border membranes of small intestine, renal proximal tubules and placenta
Also present on CNS synaptic membranes
Receptor for one strain of human coronavirus that causes many upper respiratory tract infections
Defects appear to cause various leukemias/lymphomas
Serves an important function for early CMV infection
CD13 autoantibodies are strongly associated with chronic graft versus host disease after bone marrow transplantation
Positive staining (normal): bile duct canaliculi, central nervous system synapses, endothelial cells, fibroblasts, granulocytes (most), large granular lymphocytes (some), macrophages, osteoclasts, perineurium of peripheral nerves, placenta, renal proximal tubules, small intestine
Positive staining (disease): AML M1-M5 (75-95%), M6 (usually), CML (90%); pre B ALL (7-10%), pre T ALL (rare)
 

CD14



Aka lipopolysaccharide (LPS) receptor, endotoxin receptor
Binding of LPS to CD14 on macrophages causes their activation and release of cytokines
Involved in the clearance of apoptotic cells
Also regulates IgE levels
Positive staining (normal): macrophages/monocytes (90%), granulocytes-weak (30%), Langerhans cells; dendritic cells, B cells
Positive staining (disease): B-CLL (90%), follicular center cell lymphoma (80%), diffuse large B cell lymphoma (40%); AML-M4/M5 (50-90%)
Negative staining: myeloid progenitors, AML M3, M6, M7, M0-M2 (usually)
 

CD15



Aka LeuM1, Lacto-N-Fucopentose III ceramide
Recognizes Hapten X, a carbohydrate linked to cell membrane proteins of myelomonocytic cells
Positive staining (normal): myeloid cells (90%); activated B and T cells (including infectious mononucleosis); eosinophils stain intensely
Positive staining (disease): Reed-Sternberg cells, 20% of T cell lymphomas, 5% of B cell lymphomas, 50% of carcinomas
Negative staining: erythroid cells, platelets; ALL
Micro images: Reed-Sternberg cells-figure 3A, primary pulmonary Hodgkin’s lymphoma-figure 3A
 

CD15s



Aka Sialyl Lewis X; ligand for CD62P and CD62E
Positive staining (normal): granulocytes, macrophages
 

CD15u



Aka sulfated CD15
 

CD16a



Aka Fc receptor III A
Important for Ab dependent cytotoxicity of foreign cells
If target cell has class I MHC, then NK cell's killer cell inhibitory receptor (KIR) inhibits cytolysis

Positive staining (normal): NK cells (10-20%), granulocytes, monocytes (rare), alveolar macrophages (common), T cells (some)
Negative staining: Myelodysplastic syndrome
 

CD16b



Aka Fc receptor III B
Positive staining: neutrophils
 

CD17



Aka Lactosylceramide
Binds to bacteria and may function in phagocytosis
Positive staining (normal): granulocytes, macrophages/monocytes, platelets, basophils, CD19+ B cells, tonsillar dendritic cells
 

CD18



Forms the beta 2 chain of CD11a, b, c (leukocyte adhesion molecule)
Important for adhesion and signaling in the hemaoietic system (see CD11 a-c above)
Leukocyte Adhesion Deficiency (LAD-1) caused by CD18 defect coding for common b2 subunit; patients suffer from recurrent infections
Positive staining: leukocytes
 

CD19



Response regulator that plays a dominant role in establishing signaling thresholds for antigen receptors and other surface receptors on B cells; also regulates B cell development, activation and differentiation
CD19 antibody inhibits B cell activation from anti-immunoglobulin
Coreceptor with CD21
Earliest B cell antigen in fetal tissue

Positive staining (normal): Pre B, B cells; first B cell antigen after HLA-DR, follicular dendritic cells

Negative staining: plasma cells
 

CD20



Aka L26
33kd phosphoprotein with 3 hydrophobic regions that traverse the cell membrane, creating a structure similar to an ion channel
Delivers early signal in B cell activation, allowing resting B cells to respond to later antigens
Rituximab is a chimeric murine-human anti-CD20 antibody used for treatment of B cell lymphomas
Uses: commonly used marker for B cells

Positive staining (normal): Most B cells (after CD19 and CD10 expression, before CD21/22 expression and surface immunoglobulin expression), retained on mature B cells until plasma cell development; also follicular dendritic cells

Positive staining (disease): 90% of B cell lymphomas, 40% of pre B ALL/LBL; 80% of lymphocyte predominant Hodgkin’s lymphoma, dimly expressed in T cells (benign and neoplastic), spindle cell thymomas
Negative staining: non-hemaoietic cells, most T cells, plasma cells
Micro images: large B cell lymphoma, CNS diffuse large B cell lymphoma (figure A), lymphoplasmacytic lymphoma/ Waldenström macroglobulinemia in brain-figure D
Micro images (Mod Path subscribers): post-transplant lymphoproliferative disorder
References: Mod Path 2002;15:647
 

CD21



Aka CR2, C3d receptor, EBV receptor

Binds to Epstein Barr virus and breakdown products of complement component C3

Forms a signaling complex with CD19, CD81 and CD225

Both CD21 and CD23 are dendritic cell markers

Hodgkin’s lymphoma demonstrates disruption of follicular dendritic cell-germinal cell clusters (evaluated by CD21 and CD23)

Positive staining (normal): Mature B cells, follicular dendritic cells

Micro images (AJSP subscribers): inflammatory pseudotumor-like follicular dendritic cell tumor A, B, Hodgkin’s lymphoma A, B
Micro images (Mod Path subscribers): extranodal follicular dendritic cell sarcoma
References: AJSP 2001;25:721, AJSP 2001;25:388, Mod Path 2002;15:50
 

CD22



 

Aka B lymphocyte cell adhesion molecule (BL-CAM)
May localize B cells in lymphoid tissues; binds CD45

Positive staining (normal): B cells, B-ALL

Negative staining: plasma cells
 

CD23



Aka low affinity IgE receptor
Regulates IgE synthesis by negative feedback
Triggers monokine release (TNF, IL-1, IL-6, GM-CSF) by monocytes
After physiologic germinal cell development, the follicular dendritic cell meshwork expands and follicular dendritic cells in the light zone of the germinal center become CD23 positive
CD23 also acts as B cell growth factor, promoting differentiation into plasma cells

Both CD21 and CD23 are dendritic cell markers

Positive staining (normal): Activated mature B cells expressing IgM or IgD, monocytes/macrophages, T cell subsets, platelets, eosinophils, Langerhans cells, follicular dendritic cells

Positive staining (disease): B-cell CLL/SLL
Negative staining: other B cells; mantle cell lymphoma
 

CD24



 

Promotes antigen dependent proliferation of B cells; prevents differentiation into plasma cells

Expressed at high levels in small cell lung carcinoma
Positive staining (normal): all B cells, granulocytes, kidney cells, epithelial cells
Positive staining (disease): carcinomas, most pre-B ALL/LBL, virtually all B cell lymphomas
Negative staining: plasma cells, multiple myeloma, T cells, monocytes, red blood cells, platelets
 

CD25



Aka IL-2 receptor alpha chain, exists in at least 3 forms
Limited expression may safeguard against catastrophic T-cell proliferation by immunogenic stimulus.
Positive staining: Activated B, T, macrophages
Positive staining (disease): hairy cell leukemia
 

CD26



Aka dipeptidylpeptidase IV, adenosine deaminase complexing protein 2
Costimulatory molecule in T cell activation
Cofactor with CD4 for HIV entry into cells
Positive staining (normal): Activated T, B cells, NK cells, macrophages, renal proximal tubular epithelial cells, small intestinal epithelium, biliary canaliculae, splenic sinus lining cells
Negative/dim staining: T cells in peripheral blood of mycosis fungoides patients, AJCP 2001;115:885
 

CD27



 

Marker of T cell activation
CD27/CD70 interactions also regulate B cell proliferation and T cell differentiation
Positive staining: T cells, memory B cells
 

CD28



Cell adhesion molecule; co-receptor for B cell-T cell cooperation
Promotes T cell activation
Receptor for CD80 (B7) & CD86 (BB1), found on activated B cells
Constitutive, high abundance, low affinity receptor; opposite signals are mediated by CTLA4 (CD152)
Result of T cell antigen stimulation depends on sum of effects of T cell receptor, CD28 and its ligand, CTLA4 and its ligand
CD8+, CD28+ T cells mediate antigen specific cytotoxic T cells (class I restricted) (90% of CD8+ T cells)
CD8+, CD28- T cells mediate suppressor T cells (10% of CD8+ T cells)
Positive staining (normal): CD4+ T cells (95%), CD8+ T cells (50%); activated B cells, plasma cells
Reference: 186760
 

CD29



Aka platelet GPIIa, beta-1 integrin, fibronectin receptor
Positive staining (normal): fibroblasts, platelets, T cells
 

CD30



Aka Ki-1, Ber-H2
Lymphocyte activation antigen, related to tumor necrosis factor
Doesn’t work well with B5 fixed tissue
May be involved in negative T cell selection in thymus
Interpretation: membranous staining
Positive staining (normal): granulocytes, plasma cells, activated B, T and NK cells
Positive staining (disease): infectious mononucleosis, lymphocytes infected with HIV, HTLV-1, EBV, HHV8 or hepatitis B; Reed-Sternberg cells, 90% of anaplastic large cell lymphomas, lymphomatoid papulosis, peripheral T-cell lymphomas, embryonal carcinoma of testis, primary effusion lymphoma
Micro images: Hodgkin’s lymphoma #1, #2, #3-figure 3B (primary pulmonary), #4-figure 3B, anaplastic lymphoma, embryonal carcinoma-figure 6, intratubular embryonal carcinoma-figure 4
Micro images (Hum Path subscribers): anaplastic large cell lymphoma (figure E), AIDS related primary effusion lymphoma (figure D)
 

CD31



Aka platelet endothelial cell adhesion molecule, PECAM-1
Encoded on #17
Most sensitive and specific endothelial marker in paraffin sections
Important role in diapedesis step of leukocyte emigration in inflammation; also angiogenesis
Note: don’t confuse CD31+ macrophages (granular, membranous expression) with a vascular tumor, AJSP 2001;25:1167
Sensitive for malignant vascular tumors; may be less sensitive for benign lesions
Interpretation: membranous stain (not cylasmic); endothelium is a positive internal control
Positive staining (normal): endothelium, platelets, macrophages and Kupffer cells, granulocytes, T / NK cells, lymphocytes, megakaryocytes, fibroblasts, osteoclasts, neutrophils
Positive staining (tumors): epithelioid hemangioendothelioma; epithelioid sarcoma-like hemangioendothelioma (AJSP 2003;27:48); other vascular tumors, histiocytic malignancies, plasmacytomas; rare carcinomas and sarcomas
Micro images: epithelioid angiosarcoma (figure 1A)
Micro images (AJSP subscribers): epithelioid sarcoma-like hemangioendothelioma, epithelioid hemangioendothelioma, epithelioid angiosarcoma, CD31+ macrophages, malignant histiocytosis
Micro images (Hum Path subscribers): hepatic cavernous hemangiomas (figure 2B)
Micro images (Mod Path subscribers): angiosarcoma (figure E)
References:  AJSP 2001;25:684, Mod Path 2002:15;434
 

CD32



Aka Fc gamma RII
Low affinity receptor that binds to the Fc region of IgG immune complexes
If B cells are stimulated so that surface immunoglobulin receptors are coclustered with CD32 receptors, B cells do NOT proliferative and may undergo apoptosis instead of proliferation
Positive staining: macrophages, granulocytes, B cells, eosinophils, basophils, platelets
 

CD33



Myeloid cell antigen (also CD13); a sialoadhesin that may mediate cell-to-cell adhesion, acts as a receptor that inhibits the proliferation of normal and leukemic myeloid cells
Positive staining (normal): Precursor myeloid cells; most monocytic cells, epidermal Langerhans cells (variable)
Positive staining (disease): AML M1-M5 (75-85%), M7 (variable), CML (90%); blasts (all), some ALL
Negative staining: granulocytes, mature bone marrow cells, non-myeloid cells
 

CD34



Cell-cell adhesion molecule and cell surface glycoprotein
May mediate attachment of stem cells to bone marrow extracellular matrix or directly to stromal cells
Antibodies are used to quantify and purify lymphohemaoietic stem cell / progenitor cells for research and for clinical bone marrow transplantation; however, counting CD34+ mononuclear cells may overestimate myeloid blasts in bone marrow smears due to hematogones and CD34+ megakaryocytes, Archives 2002;126:823
Interpretation:
membranous stain; endothelium acts as a positive internal control
Uses: possibly confirm chronic intestinal pseudo-obstruction, AJSP 2003;27:228
Positive staining (normal): hemaoietic progenitor cells, vascular endothelial cells (these cells are TdT+, HLA-DR+)
Positive staining (disease): alveolar soft part sarcoma, preB-ALL (75%), AML (40%), AML-M7 (most), chordoid gliomas, dendritic fibromyxolipoma, dermatofibrosarcoma protuberans, epithelioid sarcomas, gastrointestinal stromal tumors, giant cell fibroblastoma, granulocytic sarcoma, hamartomatous tumors of chronic drug resistant epilepsy, hemangiopericytomas (50%), inflammatory fibrous polyps of stomach (Hum Path 2002;33:307), Kaposi’s sarcoma (strong, diffuse in spindle cells), liposarcomas (myxoid, pleomorphic), MFH, malignant peripheral nerve sheath tumors, meningeal hemangiopericytomas, meningiomas (some), metanephric adenosarcoma of kidney (stroma only), myelodysplastic syndrome (myeloid blasts), myofibroblastoma of breast, neurofibromas, nuchal fibromas (also CD99+), papillary thyroid carcinoma, paratesticular leiomyosarcoma (30%), pleomorphic hyalinizing angiectatic tumor, pseudoangiomatous stromal hyperplasia of breast, schwannomas (usually), sclerosing liposarcoma (spindle and atypical cells), solitary fibrous tumors, synovial sarcoma (focal in 6% of monophasic tumors), blasts in transient myeloproliferative disorder
Negative staining: Ewing’s sarcoma/PNET, myofibrosarcoma of breast, inflammatory myofibroblastic tumors of stomach
Micro images: granulocytic sarcomamalignant solitary fibrous tumor, GIST and solitary fibrous tumor, GIST (figure B), CD34+ blasts and megakaryoctyes, cavernous hemangioma of spermatic cord, solitary fibrous tumor of orbit
Micro images (AJSP subscribers): hybrid DFSP-giant cell fibroblastoma, solitary fibrous tumor of kidney, metanephric adenosarcoma of kidney (stroma only), rectal GIST (figure B), paratesticular leiomyosarcoma, normal small bowel (figure 1B), normal colon (figure 1B), chronic intestinal pseudo-obstruction (figure 1B), Gardner associated fibromas, microcystic adnexal carcinoma A, B
Micro images (Mod Path subscribers): GIST (figures C, D)
Reference: Archives 2002;126:1189, AJSP 2003;27:27, AJSP 2002;26:932, AJSP 2001;25:1451, AJSP 2001;25:1194; AJSP 2001;25:645, AJSP 2001;25:464, Mod Path 2002;15:125
 

CD35



Aka CR1, C3b and C4b receptor
Mediates adherence of immune complexes coated with C4b/C3b and their transport to the fixed phagocyte systems of the spleen and liver
Cofactor for specific proteolytic cleavage of C3b and C4b by plasma serine protease factor I, which limits complement activation and produces ligands for other complement receptors
The Knops, McCoy, Swain-Langley, and York blood group antigens are located on CD35
Positive staining: granulocytes, macrophages, B cells, T cells (10%), NK cell subset, erythrocytes, follicular dendritic cells, eosinophils, glomerular podocytes, some astrocytes
Micro images (AJSP subscribers): inflammatory pseudotumor-like follicular dendritic cell tumor A, B
Micro images (Mod Path subscribers): extranodal follicular dendritic cell sarcoma (figure 7B)
Reference: AJSP 2001;25:721, Mod Path 2002;15:50
 

CD36



Aka platelet GPIV or GPIIIb; thrombospondin receptor
Scavenger receptor for 50% of oxidized LDL and shed photoreceptor outer segments
Cell adhesion molecule in platelet adhesion and aggregation, platelet-monocyte and platelet-tumor cell interaction
Site of cytoadherence of Plasmodium falciparum infected erythrocytes to microvascular endothelial cells
CD36 deficiency frequent in sub-Saharan Africa, Asia; associated surprisingly with susceptibility to severe cerebral malaria
Development of anti-CD36 antibodies can cause serious complications in multiply transfused patients (sickle cell disease)
Positive staining (normal): platelets, macrophages, endothelial cells, early erythroid cells, megakaryocytes
Positive staining (disease): AML M4-M7
Negative staining: AML M0-M2 (usually), M3
 

CD37



 

Possibly involved in signal transduction, belongs to tetraspanin family

Positive staining (normal): B cells, B cell lymphomas, low levels on T cells, neutrophils, granulocytes, monocytes
Positive staining (disease): hairy cell leukemia
 

CD38



Novel enzyme capable of catalyzing multiple reactions; two enzyme products are calcium messengers
Positive and negative regulator of cell activation and proliferation, depending on the cellular environment
Involved in adhesion between human lymphocytes and endothelial cells
Important for leukemia phenotyping and classification, targeting of immunotoxin antibody in myeloma treatment
Increases with HIV seroconversion; coexpression with CD8 associated with progression (indicates persistent viral stimulation)
Positive staining (normal): plasma cells (strong), lymphoid progenitor cells, NK cells, B and T cells, monocytes, erythroid and myeloid precursors, thymocytes, blasts, brain, muscle, kidney, liver, ovary, pancreas, placenta, testis
Positive staining (disease): lymphoma, neuroblastoma
   

CD39



Aka vascular ATP diphosphohydrolase
Plasma membrane-bound enzyme that hydrolyzes extracellular ATP and ADP to AMP
Important inhibitor of platelet activation
Positive staining (normal): B, T and NK cells, endothelial cells, placenta
 

CD40



Plays a central role in regulating cell-mediated immunity and antibody mediated immunity
May mediate inflammatory component of atherogenesis
Positive staining (normal): B cells, macrophages, dendritic cells, endothelial cells, fibroblasts, keratinocytes
Positive staining (disease): carcinomas, most B cell lymphomas, B-ALL (some)
Negative staining: plasma cells
 

CD41



Aka platelet GPIIb
Receptor for fibrinogenin, von Willebrand factor and fibronectin
Mutations cause thrombasthenia
Positive staining (normal): platelets, megakaryocytes
Positive staining (disease): AML M7, blasts in transient myeloproliferative disorder
 

CD42a



Aka platelet GPIX
CD42a-d complex is receptor for von Willebrand factor and thrombin
Actual binding site of vWf and thrombin is on CD42b
This complex mediates adhesion of platelets to subendothelial matrices exposed upon damage to endothelium and amplifies platelet response to thrombin
Absence of CD42 complex (mutations in CD42 a-c) causes Bernard-Soulier syndrome (BSS), a bleeding disorder with thrombocyenia and giant platelets
Positive staining (normal): platelets and megakaryocytes
 

CD42b



Aka platelet GPIb alpha
CD42a-d complex is receptor for von Willebrand factor and thrombin
Actual binding site of vWf and thrombin is on CD42b
Positive staining (normal): platelets and megakaryocytes
Positive staining (disease): blasts in transient myeloproliferative disorder
 

CD42c



Aka platelet GPIb beta
Positive staining (normal): platelets and megakaryocytes
 

CD42d



Aka platelet GP V
CD42d mouse monoclonal antibodies are used to detect auto- and allo-anti-platelet antibodies
Co-expression studies suggest that CD42d may be essential to form the high affinity thrombin receptor
Positive staining (normal): platelets and megakaryocytes
 

CD43



Aka leukosialin, sialophorin
Appears to be an anti-adhesive molecule mediating repulsion between leukocytes and other cells, although it may act as an adhesion molecule under other circumstances
Expression defective in Wiskott-Aldrich syndrome, although secondary to X linked genetic defect; causes defects in cytotoxic and helper T cell functions
Positive staining (normal): Most T cells, activated B cells, NK cells, granulocytes, monocytes, megakaryocytes, brain
Positive staining (disease): 80% of T cell lymphomas; coexpressed with CD20 in SLL but not benign lesions; granulocytic sarcomas, AML, most ALL's, plasmacytomas; mast cell disease (also positive for tryptase, CD68, CD117)
Micro images: granulocytic sarcoma, mantle cell lymphoma
Micro images (AJSP subscribers): chronic active myocarditis (figure B)
 

CD44



Family of cell surface glycoproteins with isoforms generated by alternate splicing of mRNA
Important in epithelial cell adhesion to hyaluronate in basement membranes and maintaining polar orientation of cells; also binds laminin, collagen and fibronectin
May help lymphomas disseminate by binding to high endothelial venules
Involved in leukocyte attachment and rolling on endothelial cells, homing to peripheral lymphoid organs and sites of inflammation and leukocyte aggregation
Uses: reactive urothelium has diffuse full thickness staining vs. carcinoma in situ, AJSP 2001;25:1074
Prognostic significance:
Colon carcinoma: overexpression of CD44v predicts an aggressive course
Endometrial carcinoma: loss of CD44 related to invasion
Lung carcinoma: loss of CD44 related to invasion
Lymphomas - diffuse large cell and B-CLL: expression associated with poor prognosis
Neuroblastoma: loss of CD44 related to invasion
Prostate cancer: loss associated with poor outcome
Urothelial neoplasms, papillary: loss of CD44 immunoreactivity (restricted to basal cell layer in normal urothelium) associated with increasing tumor grade and stage in pTa and pT1 patients, Mod Path 2000;13:1315
Positive staining (normal): white blood cells, red blood cells, breast, colon, stomach, uterus, most tissue; urothelial basal cells; reactive urothelium has diffuse full thickness staining (AJSP 2001;25:1074)
Positive staining (tumors): 80% of colorectal carcinomas; tumors or mucosa with well-developed squamous differentiation Archives 2000;124(2):212
Negative staining: platelets, hepatocytes, cardiac muscle, kidney tubular epithelium, testis, normal glandular type epithelium, well differentiated adenocarcinomas, urothelial carcinoma
Micro images: CD44s in colonic adenocarcinoma (figure B)
Micro images (AJSP subscribers): normal urothelium (figure 1D), reactive urothelium (figure 2D), reactive urothelium (figure 4D)
 

CD44h



Aka CD44s
Principal receptor for hyaluronic acid
Theoretical utility in differentiating mesothelioma since it produces abundant hyaluronic acid, but not actually useful because CD44H is reactive in 1/3 to 1/2 of adenocarcinomas, Hum Path 2002;33:953
 

CD44r



May be involved in leukocyte attachment and rolling on endothelial cells, homing to peripheral lymphoid organs and to sites of inflammation
Heterogeneous group of CD44 variant isoforms expressed constitutively in epithelial cells and monocyte lineage cells; upregulated in activated leukocytes
 

CD45



Aka leukocyte common antigen (LCA); a tyrosine phosphatase
Critical requirement for T and B cell antigen receptor-mediated activation
Target of immunosuppressive antibody treatment
Major component of glycocalyx
Negative in patients with severe combined immunodeficiency, characterized by a defect in function or B and T cell development, lymphopenia, and deficiency in humoral and cell-mediated immunity.
Different subsets of hemaoietic cells express different isoforms, which can change in response to cytokines:

CD45RA - naive/resting T cells, medullary thymocytes

CD45RO - memory/activated T cells, cortical thymocytes
Positive staining (normal): all hemaoietic cells, stronger in lymphocytes (10% of surface area)
Negative staining: red blood cells, non-hemaoietic cells, lymphoplasmacytic lymphoma, lymphoblastic lymphoma, anaplastic lymphoma, multiple myeloma, Reed-Sternberg cells
Micro images: Reed-Sternberg cells-CD45 negative, figure 3C
 

CD45RO



Aka UCHL-1
Positive staining (normal): memory and activated T cells, some B cells, granulocytes (weak), macrophages (weak), cortical thymocytes
Positive staining (disease): 75% of T cell non-Hodgkin’s lymphomas, variable T cell ALL/LBL, 25% of AML
Negative staining: Most B cell non-Hodgkin’s lymphomas, carcinomas
Micro images: nasal NK/T cell lymphoma (figure C)
 

CD46



Aka membrane cofactor protein (MCP)
Cofactor for Factor I proteolytic cleavage of C3b and C4b; prevents inappropriate complement activation, especially via alternative pathway, by limiting formation and function of C3 convertases
Receptor for measles virus and HHV-6
Has multiple isoforms
Acrosomal CD46 is exposed on sperm head at capacitation; may help fuse spermatozoa and oocyte
Positive staining (normal): all cells except erythrocytes
 

CD47



Aka integrin associated protein (IAP); one of many thrombospondin receptors
Similar to Rh-antigen
May interact with integrins and mediate intracellular calcium increase during cell adhesion
May help macrophages distinguish self from foreign substances
May have role in giant cell creation from macrophage fusion
Positive staining (normal): hemaoietic cells, epithelial cells, endothelial cells, fibroblasts, mesenchymal cells
Positive staining (disease): tumor cell lines
 

CD47R



Aka Rh related antigen
Similar to Rh-antigen; may interact with integrins
Previously CDw149
 

CD48



Mediates adhesion via its receptor, CD2
CD48-positive lymphocytes decreased in paroxysmal nocturnal hemoglobinuria
Positive staining (normal): most leukocytes, activated lymphocytes
Negative staining: neutrophils, platelets
 

CD49a



Aka very late antigen (VLA) alpha 1 chain, integrin alpha 1 chain
Integrins are integral cell-surface proteins composed of an alpha chain and a beta chain. A given chain may combine with multiple partners resulting in different integrins.
Very late activation proteins (VLA) are a family of integrins originally identified on activated human T cells, later on fibroblasts, platelets, others. Six forms, VLA1 to VLA6, have been identified, each with distinct alpha chain (numbered alpha-1 to alpha-6) associated with a common beta chain.
CD49a - Laminin and collagen receptor
Positive staining (normal): activated B and T cells, monocytes
 

CD49b



Aka very late antigen (VLA) alpha 2 chain - on T cells
Aka GPIa/IIa when expressed on platelets
Receptor for laminin, collagen, fibronectin, e-cadherin
Responsible for platelet adhesion to collagen (blood clotting), role in angiogenesis
Positive staining (normal): platelets, activated B & T cells
 

CD49c



Aka very late antigen (VLA) alpha 3 chain
Receptor for laminin, collagen, fibronectin, thrombospondin
Positive staining (normal): nonhemaoietic cells
 

CD49d



Aka very late antigen (VLA) alpha 4 chain
Receptor for fibronectin, thrombospondin, VCAM-1
Role in cell-cell interactions and cell adhesion to the extracellular matrix
Promotes (a) lymphocyte migration into tissue by strengthening lymphocyte adhesion to endothelial cells, (b) rolling of T cells in vascular lumen on VCAM-1 of endothelium, (c) homing of T cell subsets to Peyer's patches, (d) differentiation of hemaoietic precursor cells by adhesion to bone marrow stromal cells
Relevant to tumor progression and metastasis
Positive staining (normal): macrophages, T and B cells, thymocytes, eosinophils, basophils, NK cells, dendritic cells, myeloid cells, erythrocyte precursors
Positive staining (disease): melanoma cells
Negative staining: erythrocytes, platelets, neutrophils
 

CD49e



Aka very late antigen (VLA) alpha 5 chain

Fibronectin and fibrinogen receptor

Positive staining (normal): platelets, monocytes, neutrophils
 

CD49f



Aka very late antigen (VLA) alpha 6 chain
Laminin receptor
Important for formation of hemidesmosomes of stratified squamous and transitional epithelia
Positive staining (normal): epithelial cells
 

CD50



Aka ICAM-3; ligand for LFA-1 (CD54)
Provides adhesion signals important in B-T cell interactions
Important in MHC restricted interaction between T cells and target cells
Regulates leukocyte morphology
Positive staining (normal): leukocytes, epidermal Langerhans cells, endothelial cells
Negative staining: non-hemaoietic cells
 

CD51



Aka vitronectin receptor-alpha chain; beta chain of vitronectin receptor is CD61
Positive staining (normal): platelets, endothelial cells, megakaryocytes
 

CD52



Aka Campath-1
CD52 antibodies are lytic for target cells, both with human complement and via antibody dependent cellular cytotoxicity
CD52 antibodies used for long-term depletion of lymphocytes in vivo, in trials for CLL and as immunosuppressant; patients have higher risk for opportunitistic infections
Positive staining (normal): thymocytes, lymphocytes, monocytes/macrophages, eosinophils, epithelial cells lining the male reproductive tract
Positive staining (disease): most lymphoid malignancies (variable levels),
Negative staining: lymphocytes from patients with PNH, neutrophils (weaker than eosinophils)
 

CD53



Most specific and reliable pan-leukocyte marker
May transduce CD2-generated signals in T cells and natural killer cells
Positive staining (normal): leukocytes
Negative staining: platelets, red blood cells, non-hemaoietic cells
 

CD54



Aka ICAM-1 (intercellular adhesion molecule 1); ligand for LFA-1 (CD50)
Receptor for rhinovirus, malaria infected erythrocytes
Involved in adhesion of neutrophils to endothelium at site of inflammation
 
 
Reacts with CD11a / CD18 or CD11b / CD18 resulting in immune reaction or inflammation
Positive staining (normal): broad, B and T cells, monocytes, endothelial cells, epithelial cells (various)
Positive staining (tumors): keratoacanthoma (more in fully developed lesions with inflammatory infiltrate), cutaneous squamous cell carcinoma
Micro images (Mod Path subscribers): keratoacanthoma, poorly differentiated squamous cell carcinoma
Reference: Mod Path 2003;16:8
 

CD55



Aka decay accelerating factor
Binds C3bBb (alternative pathway convertase) and C4b2a (classical pathway convertase) to accelerate decay of the C3 convertases; protects against inappropriate complement activation
Receptor for CD97
Receptor for echovirus and Coxsackie B virus
Deficient in red blood cells from patients with paroxysmal nocturnal hemoglobinuria
Positive staining (normal): all hemaoietic cells and all cell types in intimate contact with complement proteins; also epithelial cells lining extracellular compartments, body fluids, extracellular matrix
 

CD56



Aka N-CAM (neural cell adhesion molecule), at #11q23
Regulates homophilic (like-like) interactions between neurons and between neurons and muscle

Also associates with fibroblast growth factor receptor and stimulates tyrosine kinase activity of receptor to induce neurite outgrowth
When neural crest cells s making N-CAM and N-cadherin and start displaying integrin receptors, cells separate and migrate
Contributes to cell-cell or cell-matrix adhesion during development
Lymphocyte activated killer phenomenon mediated by IL-2 activated CD56+, CD3-, NK cells
Prototypic marker of NK cells, also present on subset of CD4+ and CD8+ T cells

Positive staining (normal): NK cells (80-90%), activated T cells; cerebellum and brain at neuromuscular junctions, also normal neuroendocrine tissues

Positive staining (tumors): myeloma, myeloid leukemia, neuroendocrine tumors, Wilm’s tumor, adult neuroblastoma, NK/T cell lymphomas, pancreatic acinar cell carcinoma, pheochromocytoma, small cell lung carcinoma

Negative staining: PNET/Ewing’s sarcoma
Micro images: testicular NK/T cell lymphoma (figure 3C), extranodal NK/T cell lymphoma, nasal type
 

CD57



Aka Leu7
Glycoprotein with cell adhesion functions
NK cell marker and neuroendocrine marker
Subset of NK cells (note: NK cells have no TCR membrane expression or gene rearrangement)
CD16+, CD57-:  substantial NK activity
CD16-, CD57-:  no NK activity
CD16-, CD57+:  weak NK activity
CD16+, CD57+:  variable NK activity
Associated with poor prognosis in nasal lymphomas
Positive staining (normal): NK subset, T cell subset (CD2,3,5), neuroectodermal tissue, brain, prostate, proximal tubules of kidney
Positive staining (tumors): neuroectodermal tumors, small cell lung cancer (some), prostatic adenocarcinoma, nerve sheath origin lesions, metanephric adenoma, renal carcinoid tumors, some clear cell renal cell carcinomas, spindle cell thymomas (AJSP 2001;25:111, lymphomas (some)
Micro images (AJSP subscribers): metanephric adenoma (figure 4C), Wilms tumor #1 (figure 5C), #2 (figure 6C), dendritic cell neurofibroma with pseudorosettes
Reference: AJSP 2001;25:587, AJSP 2001;25:1290
 

CD58



Aka LFA-3 (lymphocyte function associated antigen); ligand for CD2
Mediates adhesion between NK and target cells, antigen presenting cells and T cells, thymocytes and thymic epithelial cells
Positive staining (normal): leukocytes, erythrocytes, endothelial cells, epithelial cells, fibroblasts
 

CD59



Aka protectin
Regulates complement mediated cell lysis by inhibiting formation of membrane attack complex (MAC)

Genetic defects that cause a reduction or loss of both CD59 and CD55 on erythrocytes produce paroxysmal nocturnal hemoglobinuria (PNH)
Incorporated into HIV envelope, protects virus and HIV infected cells against complement deposition
Expression on erythrocytes important for their survival
Positive staining (normal): most cells
 

CDw60



Antibodies provide costimulatory/comitogenic signals for T cells

Expressed on most T cells in autoimmune lesions

Positive staining (normal): platelets, T subset, thymic epithelium, activated keratinocytes, synovial fibroblasts, glomeruli, smooth muscle cells, astrocytes
 

CD60a



GD3 - carbohydrate structure
 

CD60b



9-O-acetyl-GD3 - carbohydrate structure
 

CD60c



7-O-acetyl-GD3 - carbohydrate structure
 

CD61



Aka platelet glycoprotein IIb/IIIa
Receptor for fibrinogen, fibronectin, prothrombin, thrombospondin, vitronectin, plasminogen
Mediates platelet aggregation by binding soluble fibrinogen, forming platelet plug
Defects cause Glanzmann thrombasthenia, an autosomal recessive disorder and the most common inherited platelet disease
Positive staining (normal): platelets, megakaryocytes, myeloid progenitor cells, endothelial cells
Positive staining (disease): AML M7, AML M6 (some), blasts in transient myeloproliferative disorder
Negative staining: AML M0-M5, M6 (most)
Micro images: megakaryoctyes (figures C, D)
 

CD62E



Aka E selectin; endothelial leukocyte adhesion molecule-1 (ELAM-1)
Ligand for sialyl-Lewis X
Mediates leukocyte rolling on activated endothelium at inflammatory sites, atherosclerosis, tumor cell adhesion during hematogenous metastasis
Patients with Leukocyte Adhesion Deficiency 2 syndrome, who lack sialyl Lewis X component of selectin counter-receptors, suffer recurrent pyogenic infections
Positive staining (normal): endothelial cells (after cytokine stimulation)
 

CD62L



Aka L selectin; LECAM-1
Mediates lymphocyte homing to high endothelial venules of peripheral lymphoid tissue, leukocyte rolling on activated endothelium at inflammatory sites
Positive staining (normal): B, T, NK cells, monocytes, neutrophils, eosinophils, precursors
Reference: 153240
 

CD62P



Aka P selectin; PADGEM
Interaction with CD162 mediates tethering and rolling of leukocytes on the surface of activated endothelial cells, the first step in leukocyte extravasation and migration
Mediates rolling of platelets on endothelial cells, platelet-mediated delivery of lymphocytes to high endothelial venules
Constitutive expression in inflammation may contribute to tissue destruction, atherogenesis and thrombosis
May be reduced in gray platelet syndrome, 139090
Redistributes to the plasma membrane during platelet activation and degranulation.

Positive staining (normal): platelets, megakaryocytes, activated endothelial cells
 

CD63



Aka lysosomal-membrane-associated glycoprotein 3, LAMP-3, melanoma associated antigen, NKI-C3
Intracellular lysosomal/endosomal/granule protein, in Weibel-Palade bodies of vascular endothelium
Marker of platelet activation (transported to surface after activation)
Associated with early stages of melanoma progression
Positive staining (normal): activated platelets, macrophages, fibroblasts, osteoclasts, endothelium, smooth muscle, neural tissue (brain white matter and peripheral nerves), synovial lining cells
Positive staining (tumors): melanoma
 

CD64



 

Aka Fc gamma RI 
High affinity receptor binds to Fc region of IgG

Important in phagocytosis via receptor-mediated endocytosis of IgG-antigen complexes
Mediates antigen capture for presentation to T cells, antibody-dependent cellular cytotoxicity, release of cytokines and reactive oxygen intermediates
Positive staining (normal): Macrophages/monocytes, activated granulocytes, dendritic cells, early myeloid cells
Positive staining (disease): AML M0-M2 (variable); M3 (usually); M4, M5
Negative staining: AML M7
 

CD65



Aka VIM2, ceramide-dodecasaccharide
Adhesive molecule that appears to be significant risk factor for extravascular AML infiltration
Positive staining (normal): myeloid cells, monocytes
 

CD65s



Widely used for acute leukemia cell typing and to identify a subset of pre-pre-B ALL
Aka sialylated-CD65
May inhibit phagocytosis
Positive staining (normal): granulocytes, monocytes
Positive staining (disease): myeloid leukemia cells
 

CD66a



Aka CEACAM1, biliary glycoprotein, BGP, C-CAM
Primordial protein of carcinoembryonic antigen (CEA) family
Cell adhesion molecule capable of activating neutrophils; may regulate CD11/CD18 activity
Receptor for Neisseria gonorrhea and N. meningitidis
Downregulated in colorectal, endometrial and hepatocellular carcinomas; supplementation may cause tumor regression in vitro or in rodents
Downregulated in Gleason grade 4/5 prostate carcinoma, Hum Path 2002;33:290
Positive staining (normal):
granulocytes, epithelial cells, prostate glands and ducts (dense), bile canaliculi between liver cells
Positive staining (disease): low grade prostatic carcinoma
Negative staining: prostate carcinoma, Gleason grade 4/5
Micro images (Hum Path subscribers): Prostate: A-normal, B-Gleason grade 3, C-Gleason grade 4, normal liver (figure F)
 

CD66b



Aka CEA gene member 6; formerly CD67
Capable of activating neutrophils; may regulate CD11/CD18 adhesion activity

Positive staining (normal): granulocytes
Positive staining (disease): chronic myelogenous leukemia

 

CD66c



Aka noncross reactive antigen (NCA)
Capable of activating neutrophils; may regulate CD11/CD18 adhesion activity
Positive staining (normal): granulocytes
 

CD66d



Capable of activating neutrophils and functions as a receptor for Neisseria gonorrhea and N. meningitidis
May play a signaling role and regulate adhesion activity of CD11/CD18 in neutrophils
Positive staining (normal): granulocytes
 

CD66e



Aka CEA, carcinoembryonic antigen
May play a role in the process of metastasis of cancer cells
Serum marker of tumor burden, relapse
Removed by hepatic Kupffer cells via a specific receptor.
Uses: 85% sensitive, 96% specific for lung adenocarcinomas vs. mesotheliomas; diffuse cylasmic staining with membrane enhancement
Positive staining (normal): biliary tract, colon (fetal), epithelial cells (apical surfaces), GI adenocarcinomas (endodermally derived), granulocytes, small intestinal crypts; small intestinal goblet cell mucin (not intracylasmic)
Positive staining (tumors): colonic and lung adenocarcinoma, medullary thyroid carcinoma
Variable staining: breast carcinoma, endometrial carcinoma, neuroendocrine carcinoma, urothelial carcinoma
Negative staining: hepatocellular carcinoma, mesothelioma, ovarian carcinoma, prostate adenocarcinoma, renal cell carcinoma, thyroid carcinoma other than medullary
 

CD66f



Aka pregnancy-specific glycoprotein
May be involved in immune regulation, protection of fetus from maternal immune system
Low levels in maternal blood predict spontaneous abortion
Positive staining (normal): syncytiotrophoblasts, fetal liver, myeloid cell lines
Reference: 176390
 

CD67



Recognizes non-specific cross-reactive antigens present on granulocytes
May have role in neutrophil activation
 

CD68



Aka KP-1
May have role in macrophage phagocytic activities
Specific to lysosomes, not cell lineage
Positive staining (normal): macrophage/monocytes, basophils, dendritic cells, mast cells, myeloid cells, CD34+ progenitor cells, neutrophils, osteoclasts, activated platelets, B and T cells
Positive staining (tumors): AML-M4/M5, angiosarcoma (granular cell type), B cell lymphoma (some), giant cell angioblastoma, granular cell tumors, hairy cell leukemia, histiocytic sarcoma, interdigitating dendritic cell sarcoma (AJSP 2002;26:530), Langerhans cell histiocytosis, mastocytosis, mast cell disease (also positive for tryptase, CD43, CD117), melanoma (some)
Micro images: multinucleated giant cell in thyroid gland giant cell granuloma (figure C), plexiform fibrohistiocytic tumor, Rosai-Dorfman disease#1#2-figure D
Micro images (AJSP subscribers): histiocytic lymphoma (figure A), histiocytic sarcoma (figure A), giant cell angioblastoma #1 (figure 5D), #2 (figure 6D)
Micro images (Mod Path subscribers): Kupffer cells in normal liver, Kupffer cells in severe non-alcoholic steatohepatitis (figure B)
Reference: AJSP 2001;25:1372, AJSP 2003;27:258, Mod Path 2002;15:699
 

CD69



Aka activation inducer molecule (AIM), early activation antigen (EA-1)
Earliest inducible cell surface glycoprotein acquired during lymphoid activation
Involved in early events of T cell, NK cell, monocyte and platelet activation
Associated with Th-1 T cell differentiation and associated cytokines (IL-2, TNF-alpha, interferon-gamma), Hum Path 2002;33:330
Highly expressed on T cells from inflammatory infiltrates of rheumatoid arthritis, viral hepatitis, autoimmune thyroid disorders;

Positive staining (normal): activated T cells, B cells, NK cells, neutrophils, eosinophils, epidermal Langerhans cells
Positive staining (disease): T cell lymphomas (angioimmunoblastic, Lennert’s, mycosis fungoides/Sezary syndrome)
Negative staining: anaplastic large cell lymphoma
Micro images (Hum Path subscribers): A-tonsil, B-peripheral T cell lymphoma NOS, C-anaplastic large cell lymphoma (H&E, frozen, paraffin)
 

CD70



Aka CD27 ligand
Role in T cell activation; induces T cell proliferation and enhances generation of cytolytic T cells
Positive staining (normal): activated B, T cells
Positive staining (disease): Reed-Sternberg cells
 

CD71



Aka transferrin receptor
Present on actively proliferating cells; essential for iron transport into proliferating cells (benign and malignant)
Ferrotransferrin binds CD71 at neutral pH, is internalized to an acidic endosomal compartment
Iron-free apotransferrin remains bound to CD71 at pH 5, is returned to cell surface, where pH rises to 7.4.
At neutral pH, apotransferrin loses affinity for receptor, is released into circulation, allowing a new cycle to begin
Positive staining (normal): all proliferating cells plus iron requiring cells: reticulocytes, erythroid precursors, capillary endothelium in brain
Positive staining (disease): AML M6, primary effusion lymphoma
 

CD72



Cell surface protein expressed exclusively on B cells; may control B cell proliferation
Associated with CD5
Positive staining (normal): B cells
Positive staining (disease): hairy cell leukemia
 

CD73



Aka ecto-5'-nucleotidase, PI-linked
Catalyses dephosphorylation of purine and pyrimidine ribo- and deoxyribonucleoside monophosphates to their corresponding nucleosides
Mediates costimulatory signals in T cell activation, lymphocyte adhesion to endothelium
May be lymphocyte maturation marker
High levels are poor prognostic factors in leukemia/lymphomas
Positive staining (normal): B and T cell subset; endothelial cells, on follicular dendritic cells, epithelial cells
Positive staining (disease): acute T cell leukemia, CLL, ALL
 

CD74



Gamma chain antigen associated with MHC class II antigen
In synthesis of class II antigens of MHC, newly synthesized alpha and beta chains form stable complex with gamma chains in the endoplasmic reticulum; then transported to Golgi, where gamma chain dissociates
Positive staining (normal): B-cells, activated T-cells, macrophages, activated endothelial and epithelial cells
 

CD75



Aka lactosamines; LN-1
Ligand for CD22
Involved in cell adhesion
Positive staining (normal): B cells, T cells, erythrocytes
Positive staining (disease): “popcorn cells” of lymphocyte predominance Hodgkin disease
Micro images: lymphocyte predominance Hodgkin disease
Reference: Archives 2002;126:862
 

CD75s



Alpha-2,6-sialylated lactosamines (formerly CDw75 and CDw76)
 

CDw76



 

Deleted at 7th HLDA Workshop; see new CD75s

 

CD77



Aka globotriaosylceraminde, pK blood group
Binds to Shiga toxin (produced by Shigella dysenteriae), verotoxin 1 (produced by E. coli), CD19
Positive staining (normal): B cells
Positive staining (disease): Burkitt's lymphoma
 

CDw78



 

Deleted at 7th HLDA Workshop

 

CD79a



Encodes the Ig-alpha protein of the B-cell antigen receptor; receptor also includes Ig-beta protein, surface immunoglobulin
Expressed early in B-cell differentiation (often positive when mature B-cell markers are negative); also expressed in plasma cells
Uses: positive in acute lymphoblastic leukemia, small B cell lymphoproliferative disorders when CD20 may be negative; more consistently preserved in infarcted lymphomas than CD20, Archives 2003;127:60
Positive staining: B cell lymphomas, lymphocyte-predominant Hodgkin lymphoma, classic Hodgkin lymphoma
Micro images: Warthin-Finkeldey giant cells in measles related appendicitis (Figure C), infarcted lymphomas, figures 2 & 6
 

CD79b



Encodes the Ig-beta protein of the B-cell antigen receptor; receptor also includes Ig-alpha protein, surface immunoglobulin
 

CD80



Aka B7-1, BB1
Ligand for T cell marker CD28 or CTLA4 (CD152)
Co-regulator of T cell activation with CD86
Has critical role in autoimmune, humoral, and transplant responses
Positive staining (normal): activated B cells, T cells, macrophages, dendritic cells
Reference: 112203
 

CD81



Aka Target of an Anti-Proliferative Antibody (TAPA1)
Antibodies against TAPA1 induce homotypic aggregation of cells and can inhibit their growth
Member of CD19/CD21/Leu-13 signal transduction complex; regulates cell growth in unknown manner
May be site of binding of Hepatitis C virus
Positive staining (normal): lymphocytes, endothelial cells, epithelial cells
Negative staining: erythrocytes, platelets, neutrophils
 

CD82



Aka prostate cancer antimetastasis gene KAI1, 'kang ai' (Chinese for anticancer).
Metastasis suppressor gene; downregulated in tumor progression of cancers
Expression correlates with p53 expression
Associates with CD4 or CD8 and delivers costimulatory signals for T cell receptor pathway
Activation antigen for T cells
Positive staining (normal): activated/differentiated hemaoietic cells
Negative staining: erythrocytes
Reference: 600623
 

CD83



Summary: Marker for dendritic cells
May assist in antigen presentation or cellular interactions that follow lymphocyte activation.
Positive staining (normal): dendritic cells, Langerhans cells, lymphocytes
Positive staining (disease): Churg-Strauss syndrome myocarditis in inflammatory infiltrates, Archives 2003;127:98
Micro images: Churg-Strauss syndrome myocarditis
Reference: GeneCards
 

CD84



Summary: Homophilic adhesion molecule that enhances IFN-gamma secretion
Positive staining (normal): B cells, thymocytes, T cell subset, monocytes/macrophages, platelets
Reference: GeneCards
 

CD85



Summary: Marker of plasma cells and hairy cell leukemia
Aka LILRB1

ILT/LIR family
Inhibitory MHC class I receptor prevents killing by NK and T cells

Also inhibits B cells activated by antigen receptor and myelomonocytic cells activated by HLA-DR
Positive staining (normal): plasma cells (strong), mantle zone, germinal center B cells, T cell subset, NK cell subset; dendritic cells
Positive staining (disease): hairy cell leukemia (strong)
Reference: GeneCards
 

CD85a-ILT5/LIR3
CD85b-ILT8
CD85c-LIR8
CD85d-ILT4/LIR2, MIR10
CD85e-ILT6/LIR4
CD85f-ILT11
CD85g-ILT7
CD85h-ILT1/LIR7
CD85i-LIR6
CD85j-ILT2/LIR1, MIR7
CD85k-ILT3/LIR5
CD85l-ILT9
CD85m-ILT10
 

CD86



Summary: Costimulates IL-2 production and T cell proliferation
Aka B7-2
Ligand for CD28 (CD80 also binds CD28), CD152 (CTLA4)
Induction of an immune response requires T cells to receive 2 sets of signals from antigen presenting cells. The first is delivered through the T-cell receptor complex, while the second is provided by the B-cell activation antigens B7-1, or CD80 and B7-2, or CD86 by interaction with the T-cell surface molecules CD28 and CTLA4
Positive staining (normal): interdigitating dendritic cells in T zones of secondary lymphoid organs, Langerhans cells, peripheral blood dendritic cells, memory B cells, germinal center B cells, monocytes (higher levels after g-IFN), endothelial cells, activated T cells
Reference: GeneCards
 

CD87



Summary: Receptor for urokinase plasminogen activator (uPA), which converts plasminogen to plasmin

Subject to negative feedback regulation by uPA, which cleaves it into an inactive form

Implicated in metastasis - receptors for uPA and plasmin are found at leading edge of tumor cells; plasmin causes hydrolysis of extra-cellular matrix proteins in the path of cellular invasion
May have adherence and chemotaxis functions
Positive staining (normal): T-cells, NK cells, monocytes, neutrophils (higher after activation), endothelial cells, fibroblasts, smooth muscle cells, keratinocytes, placental trophoblasts, hepatocytes
Positive staining (tumors): carcinomas of breast, colon and prostate; melanoma
Reference:  GeneCards
 

CD88



Summary: receptor for C5a, the chemotactic and inflammatory peptide anaphylatoxin
Stimulates chemotaxis, granule enzyme release and superoxide anion production
Reduced levels in HIV patients
Positive staining (normal): granulocytes, macrophages/monocytes, dendritic cells, astrocytes, microglia
Reference:  GeneCards
 

CD89



Summary: IgA Fc receptor, binds IgA and eliminates IgA coated targets
Induces phagocytosis, degranulation, respiratory burst and killing of microorganisms
Positive staining (normal): granulocyte lineage, monocyte lineage, activated eosinophils, alveolar and splenic macrophages
 

CD90



Summary: May mediate differentiation of hemaoietic stem cells and synaptogenesis in the CNS
Aka Thy-1
CD34+CD90+ cells include hemaoietic stem cells that serve as autologous grafts to replace the bone marrow in patients with malignancies
Positive staining (normal): hemaoietic stem cells, neurons, connective tissue
 

CD91



Summary: low density lipoprotein receptor-related protein 1; aka alpha-2-macroglobulin receptor
Binds to apoE-containing lipoproteins and mediates chylomicron remnant clearance from the plasma
Also a cell surface receptor for heat shock proteins, Archives 2003;127:178

Positive staining (normal): fibroblasts, dendritic cells, macrophages; liver, brain, lung
Micro images: psoriasis

 

CDw92



May regulate dendritic cell function
Positive staining (normal): leukocytes, endothelial cells
 

CD93



Positive staining (normal): granulocytes, monocytes, endothelial cells
Positive staining (disease): AML blasts
 

CD94



Inhibits NK cell function
Positive staining (normal): NK cells, gamma/delta and alpha/beta T cells
 

CD95



Summary: activates apoptosis when bound by Fas ligand (FasL, CD178)
Aka FAS, APO-1
Receptor for FasL; when activated, FADD (Fas-associated death domain, a separate protein from Fas) recruits caspase-8 to the receptor; resulting “death-inducing signaling complex” performs caspase-8 proteolytic activation; activated caspase-8 initiates a subsequent cascade of caspases mediating apoptosis
Fas-FasL system mediates extra-thymic self-tolerance (FasL+ cells induce apoptosis in infiltrating Fas+ lymphocytes), T cell mediated cytotoxicity, halting of immune response
Mutations cause loss of regulation of B lymphocytes, predisposing to systemic autoimmunity (SLE); Fas mutant mice develop lymphadenopathy and systemic autoimmune disease
Downregulation may cause reduction in CD4+ T cells in HIV, Archives 2002;126:28
Positive staining (normal): activated B cells, activated T cells (initially extra but nonfunctional Fas), resting T cells (low levels), breast, vaginal, endometrial and ovarian epithelium
Positive staining (disease): thyroid epithelial cells in Hashimoto’s thyroiditis, Reed-Sternberg cells in classic Hodgkin’s lymphoma, AJSP 2001;25:388, Barrett’s esophagus, esophageal adenocarcinoma
Negative staining: normal gastric mucosa
References: GeneCards
Images: Apoptosis pathway chart, Fas expression in lymph nodes of HIV patients
Micro images (Hum Path subscribers): benign tamoxifen-exposed postmenopausal endometrium
 

CD96



Aka T cell activated increased late expression (TACTILE)
May be involved in adhesion of activated T and NK cells late in immune response
Positive staining (normal): activated T cells
 

CD97



Binds to CD55 and G protein-coupled receptors
May be involved in cell adhesion and signaling processes early after leukocyte activation
Highly expressed at sites of inflammation in skin, lung and rheumatoid arthritis.
Positive staining (normal): activated T > B cells, monocytes/macrophages, dendritic cells, granulocytes
Positive staining (tumors): thyroid carcinomas, GI adenocarcinomas
Negative staining: microglia
 

CD98



Amino acid transporter, aka SLC3A2
Associated with function of pancreatic islet cells, thyroid C cells and parathyroid cells
Also involved in normal and neoplastic cell growth
Upregulated on leukocytes in inflammatory lesions, strongly expressed by neoplastic cells.
Positive staining (normal): broad
Positive staining (tumors): transformed cells
 

CD99



Summary: relatively non-specific marker for Ewing’s sarcoma and T cell lymphoma
Aka MIC2, O13
Associated with EWS-FLI1 fusion transcript, t(11;22)(q24;q12), causing FLI-1 protein overexpression
Interpretation: distinct membranous staining for Ewings/PNET; cylasmic for other tumors
Positive staining (normal): ovarian granulosa cells, pancreatic islets, infant thymus, Sertoli cells
Positive staining (tumors): T cell acute lymphoblastic lymphoma, calcifying aponeurotic fibroma, Ewing's sarcoma/PNET (95% sensitive), gastrointestinal stromal tumor, intraabdominal desmoplastic small round cell tumor (23-35%), leukemia cutis, nuchal fibromas, perineuroma (myxoid sclerosing type), rhabdomyosarcoma (membranous staining, AJSP 2002;26:1175), sinonasal undifferentiated carcinoma (rare, AJSP 2001;25:156), small cell carcinomas of lung (rare), solitary fibrous tumor, synovial sarcoma (poorly differentiated, monophasic and myxoid types), Wilm’s tumors (some), endometrial stromal tumors with sex cord differentiation
Negative staining: adult neuroblastoma
Micro images: GIST vs. solitary fibrous tumor
Micro images (AJSP subscribers): PNET of pancreas (figure B), Ewings sarcoma/PNET of kidney#1, #2, sinonasal undifferentiated carcinoma
Micro images (Hum Path subscribers): Ewings sarcoma of esophagus
Micro images (Mod Path subscribers): PNET of dura (figure C)
Reference: Archives 2002;126:1189, AJSP 2002;26:1040, Mod Path 2002;15:673
 

CD100

Increases CD45 induced T cell adhesion; down-regulates B cell expression of CD23
Positive staining (normal): most hemopoietic cells, increased expression after T cell activation
Negative staining: immature bone marrow cells
 

CD101

Positive staining (normal): monocytes, granulocytes, dendritic cells, activated T lymphocytes
 

CD102

Aka ICAM-2
Provides costimulatory signal in immune response; important in lymphocyte recirculation
Positive staining (normal): resting lymphocytes, monocytes, platelets, vascular endothelial cells
Positive staining (tumors): some lymphomas
Negative staining: neutrophils
 

CD103

Aka human mucosal lymphocyte antigen 1, integrin alphaE chain
Useful marker for intraepithelial lymphocytes (normal or tumoral), although also expressed by activated lymphocytes
Positive staining (normal): intraepithelial lymphocytes, some lamina propria T lymphocytes in the intestine
Positive staining (tumors): hairy cell leukemia; AML (many), enteropathy-associated T cell lymphomas, adult HTLV-1 associated T cell leukemia
 

CD104

Aka integrin beta 4 chain
Positive staining (normal): thymocytes
 

CD105

Aka endoglin
Regulatory component of TGF-beta receptor complex; mediates cellular response to TGF-beta 1
Target gene for Hereditary Hemorrhagic Telangiectasia type I; each affected family has a different mutation
Positive staining (normal): activated monocytes, endothelial cells; erythroid precursors in marrow; syncytiotrophoblasts, cytotrophoblasts in first trimester (transient expression)
 

CD106

Aka VCAM-1; alpha 4 beta 1 ligand
Adhesion molecular found in stimulated endothelium that plays a role in migration of white bloo--
 

CD107a

Also called lysosome-associated membrane protein 1 (LAMP-1)
Enclodes a membrane glycoprotein that provides selectins with carbohydrate ligands
May play a role in tumor metastasis, as highly metastatic tumor cells express more lamp molecules on their cell surface
Present in lysosomes, degranulated platelets, activated neutrophils, T cells and endothelium
References: (OMIM) - 153330
 
CD107b

Also called lysosome-associated membrane protein 2 (LAMP-2)
Enclodes a membrane glycoprotein that provides selectins with carbohydrate ligands
May play a role in tumor metastasis, as highly metastatic tumor cells express more lamp molecules on their cell surface
May protect or maintain lysosomes
Defects cause various glycogen storage diseases
Present in lysosomes, degranulated platelets, weakly in activated neutrophils and endothelium
References: (OMIM) - 309060
 

CD108

Also called SEMA7A, John-Milton-Hagen (JMH) human blood group antigen
A semaphorin
Potent stimulator of cytokine production, chemotaxis and superoxide release in monocytes; may have adhesion function; may modulate immune response
Autoantibodies are common, and associated with loss of JMH antigen expression
Deficiency may be associated with a rare form of congenital dyserythropoietic anemia
Expressed on erythrocytes, lymphoblasts, lymphocytes (low levels)
 

CD109

Glycophosphatidylinositol-linked glycoprotein
Carries the biallelic platelet-specific Gov antigen system, implicated in refractoriness to platelet transfusion, neonatal alloimmune thrombocyenia, and posttransfusion purpura
Expressed on subset of hemaoietic stem and progenitor cells and on activated platelets and T cells
 

CD110

Aka thrombopoietin receptor (TPO-R), myeloproliferative leukemia virus oncogene (MPL)
Binding to thrombopoietin induces megakaryocyte proliferation and differentiation and prevents apoptosis
Mutations found in some patients with congenital amegakaryocytic thrombocyenia, a disease characterized by severe congenital thrombocyenia with variable bleeding tendency and absence of megakaryocytes in the bone marrow
Positive staining (normal): hemopoietic stem and progenitor cells, megakaryocytes and progenitors, platelets
 

CD111

Aka poliovirus receptor related 1 (PRR1), nectin1
Widely expressed adhesion molecule that is a component of the adherens junction; receptor for herpes simplex viruses 1 and 2
Positive staining (normal): cells from myeloid, monocyte, megakaryocytes and erythroid lineage, epithelial cells, neurons, endothelium
 

CD112

Aka poliovirus receptor related 2 (PRR2)
Adhesion molecule that is a component of the adherens junction; receptor for herpes simplex virus
Positive staining (normal): cells from myeloid, monocyte, megakaryocytes lineage, epithelial cells, neurons, endothelium
 

CD113

Reserved for future use
 

CD114

Aka granulocyte colony-stimulating factor receptor, G-CSFR
Specific regulator of myeloid proliferation and differentiation
Mutations present in some patients with severe congenital neutropenia
Positive staining (normal): granulocytes (all), monocytes, platelets, endothelium, placenta, trophoblastic cells
Positive staining (tumors): cultured tumor cells
Negative staining: eosinophils, lymphocytes, erythrocytes
 

CD115

Aka c-fms, receptor for macrophage colony stimulating factor, CSF-1R
Localized on cylasmic membrane; mediates biologic activity of CSF-1
v-fms is a viral oncogene present in the feline McDonough sarcoma virus (has several substitute mutations)
Related to platelet derived growth factor receptor, c-kit, vascular endothelial growth factor receptor, fibroblast growth factor receptor, high affinity nerve growth factor (TrkA)
Deficiency causes reduced osteoclasts and macrophages, abnormal bone remodeling and osteopetrosis, abnormal breast development and decreased fertility
Positive staining (normal): macrophages and precursors, osteoclasts, placental trophoblast, breast tissue, microglia, neurons, astrocytes
Positive staining (tumors): 10% AML, some endometrial, ovarian and breast cancers, vascular smooth muscle cells in atheromas, choriocarcinoma cells
 

CD116

GM-CSF receptor alpha chain
Primary binding subunit of GM-CSF receptor
Positive staining (normal): monocytes, neutrophils, eosinophils, fibroblasts, endothelial cells, dendritic cells
 

CD117

Summary: proto-oncogene activated in GIST tumors
Aka c-kit, stem cell factor receptor
Gene at 4q11-21
Receptor for kit protein, a 145 kD tyrosine kinase growth factor receptor protein important for development and survival of mast cells, hemopoietic stem cells, melanocytes, germ cells, interstitial cells of Cajal
Has activating or gain of function mutations in most GIST tumors, often at exon 11, less often at exons 9 and 13, Hum Path 2002;33:484
Molecular images (Hum Path subscribers):
image1
Kit signaling pathways (Hum Path subscribers): chart1
Tyrosine kinase activity of c-kit in GIST and bcl-abl overexpression in CML are inhibited by imatinib mesylate (Gleevec, STI571), a tyrosine kinase inhibitor used to treat these diseases, Hum Path 2002;33:466
Uses:
confirming diagnosis of GIST (but see other CD117+ tumors below), possibly confirm chronic intestinal pseudo-obstruction, AJSP 2003;27:228
Interpretation: should be strong and diffuse cylasmic staining, like the positive control
Positive staining (normal): interstitial cells of Cajal, hemopoietic progenitor cells, melanocytes, embryonic/fetal brain, endothelium, gonads, mast cells, breast epithelium, germ cells
Positive staining (tumors): AML, angiomyolipoma (AJSP 2002;26:493), angiosarcomas (50%), clear cell sarcoma, CML, epithelioid sarcoma, Ewing sarcoma, gastrointestinal autonomic tumors, gastrointestinal stromal tumors (GIST), granulocytic sarcoma, Hodgkin’s lymphoma (some Reed-Sternberg cells), intraabdominal fibromatosis (depends on antibody used, AJSP 2001;25:549), mast cell disease (also positive for tryptase, CD43, CD68); melanoma, mesenteric fibromatosis (variable, AJSP 2002;26:1296), metanephric adenosarcoma (AJSP 2001;25:1451), omental mesenchymal tumor, osteosarcoma, rhabdomyosarcoma, sclerosing mesenteritis (variable), seminomas /dysgerminomas, small cell lung cancer (Hum Path 2002;33:1182), synovial sarcoma (~10%, usually cylasmic staining), adenoid cystic carcinoma of salivary gland (strong staining)
Negative staining: alveolar soft part sarcomas, desmoplastic small round cell tumors, glomus tumors, leiomyomas (retroperitoneal, colorectal), leiomyosarcomas, myxomas (cardiac), schwannomas  (colorectal), smooth muscle tumors of uncertain malignant potential, solitary fibrous tumors
Micro images: rhabdomyosarcoma of pulmonary trunk, GIST vs. solitary fibrous tumor, malignant stromal tumor of gallbladder (figure 4),
Micro images (AJSP subscribers): GIST (site unspecified), rectal GIST (figure A), metanephric adenosarcoma of kidney (stroma only), normal small bowel (figure 1A), normal colon (figure 2A), chronic intestinal pseudo-obstruction (figure 3A), intraabdominal fibromatosis (variable results with different antibodies)- #1, #2, pediatric synovial sarcomas, pediatric osteosarcomas, pediatric Ewing’s/PNET
Micro images (Hum Path subscribers): GIST #1, #2, #3, #4 (figure A), small cell lung cancer of lung (A: H&E, B: control-GIST, C: 2+ staining, D: 1+ staining)
Micro images (Mod Path subscribers): GIST (figures G, H), interstitial cells of Cajal in patient with multiple GIST tumors
References: Archives 2002;126:1189, AJSP 2002;26:486
 

CD118

Reserved for interferon alpha / gamma receptor
 

CDw119

Interferon gamma receptor
Positive staining (normal): macrophages, B cells
 

CD120a

Aka TNFR1, receptor for tumor necrosis factor alpha and beta, type I
Receptor binding to ligand causes apoptosis
 

CD120b

Aka receptor for tumor necrosis factor (TNF) alpha and beta, type II
 

CD121a

Aka Interleukin 1 receptor (IL-1R) type I, IL1-alpha
Interleukin-1, an inflammatory mediator, consists of 2 separate but related proteins, IL1-alpha and IL1-beta
Positive staining (normal): T cells, thymocytes, fibroblasts, endothelial cells
 

CDw121b

Aka Interleukin 1 receptor (IL-1 R) type II, IL1-beta
May inhibit IL1 activity by acting as a decoy target for IL1
Positive staining (normal): B cells, macrophages
 

CD122

Aka Interleukin 2 receptor beta chain (IL-2R beta)
Critical component of IL-2 and IL-15-mediated signaling
Positive staining (normal): NK cells, B cells, T cells, monocytes
 

CD123

Aka Interleukin 3 receptor alpha subunit
Associates with the GM-CSF receptor (GMR beta)
Positive staining (normal): plasmacytoid monocytes (bright with flow cytometry, AJSP 2002;26:852)
 

CD124

Aka Interleukin 4 receptor
Receptor subunit for Interleukin-4 and 13
Positive staining (normal): mature B cells, T cells; hemopoietic precursors; fibroblasts, endothelial cells
 

CDw125

Aka Interleukin 5 receptor alpha subunit
Therapeutic target of eosinophilic inflammation involved in bronchial asthma
Positive staining (normal): eosinophils, activated B cells, basophils
 

CD126

Aka Interleukin 6 receptor
Continuous expression of IL-6 and CD130, ligands for CD126, causes hypergammaglobulinemia, glomeruloproliferative nephritis and lymphoid infiltration in some organs
Dysregulated stimulation may cause myeloma and plasmacytoma
Positive staining (normal): T cells, monocytes, activated B cells, hepatocytes
 

CD127

Aka Interleukin 7 receptor
Positive staining (normal): B cell precursors, most T cells, monocytes
 

CDw128a

Aka Interleukin 8 receptor alpha subunit, CXCR1
Chemokine receptor, powerful neutrophil chemotactic factor
Positive staining (normal): neutrophils, basophils, T cell subset, monocytes, keratinocytes
 

CDw128b

Aka Interleukin 8 receptor beta subunit, CXCR2
Chemokine receptor, powerful neutrophil chemotactic factor, particularly to sites of inflammation
Binds multiple CXC chemokines including IL-8
Positive staining (normal): mature granulocytes, projection neurons, neuroendocrine cells (various)
Positive staining (tumors): carcinoids, atypical carcinoids, metastatic carcinoids, pituitary adenomas, pheochromocytomas, medullary carcinomas
Negative staining: small cell carcinoma of lung/cervix, large cell lung neuroendocrine carcinoma, Merkel cell carcinoma, neuroblastoma, melanoma
 

CD129

Reserved for Interleukin 9 receptor
 

CD130

Aka gp 130
Required for transducing biological activities of interleukin-6, interleukin-11, leukemia inhibitory factor, ciliary neurotrophic factor, oncostatin M, and cardiotrophin-1
In human, IL-6 and oncostatin M dependent activation of gp130 are involved in multiple myeloma
Positive staining (normal): almost all cell types (low levels)
 

CDw131

Aka common beta subunit
Does not bind any cytokine by itself, but is a component of the high affinity IL-3, GM-CSF and IL-5 receptors
Defective CDw131 is associated with protein alveolar proteinosis
Positive staining (normal): myeloid (early and mature), early B cells
 

CD132

Aka common cytokine receptor gamma chain - receptor for IL-2, IL-4, IL-7, IL-9 and IL-15
Mutation in humans causes X-linked severe combined immunodeficiency (no T cells, no NK cells)
CD132 is a target molecule for gene therapy for X-SCID
Positive staining (normal): T cells, B cells, NK cells, monocytes/macrophages, neutrophils
 

CD133

Aka prominin-like 1, AC 133
Alternative to CD34 in selecting hemopoietic stem and progenitor cells for transplantation studies
Localized to microvilli and other plasma membrane protrusions
Positive staining (normal): CD34 bright hemopoietic stem and progenitor cells, neural and endothelial stem cells, other primitive cells such as retina, villous and extravillous cytotrophoblast, syncytiotrophoblast
Positive staining (tumors): retinoblastoma, hemangioblasts, developing epithelium
Negative staining: adult epithelial tissue, villous stroma
 

CD134

Aka tax-transcriptionally activated glycoprotein 1 receptor, OX40 antigen, lymphoid activation antigen
 

CD135

Aka FMS-like tyrosine kinase 3, flt3
Growth factor receptor for early hemopoietic progenitors
Positive staining (normal): multipotential, myelomonocytic, and primitive B cell progenitors
Positive staining (tumors): most AML, ALL and CML
 

CDw136

Aka macrophage stimulating protein receptor, msp receptor
May regulate ciliary beat frequency in epithelial cells
Positive staining (normal): skin, kidney, lung, liver, intestine, and colon
 

CDw137

Costimulator of T cell proliferation
Positive staining (normal): T cells, especially CD45RA and CD45R0; also B cells, monocytes, epithelial cells
 

CD138

Aka heparan sulfate proteoglycan, syndecan-1
Mediates cell adhesion, growth factors; associated with late stage of B cell differentiation
Integral membrane protein is a receptor for extracellular matrix
Loss of CD138 expression is associated with tumor aggressiveness in squamous cell carcinoma (SCC) of head and neck and larynx; levels also reduced in invasive SCC but not in SCC-in situ
Interpretation: membranous staining
Positive staining (normal): B cell precursors, plasma cells, stratified squamous epithelium
Positive staining (tumors): keratoacanthoma, myeloma, primary effusion lymphoma, pyothorax associated lymphoma
Negative staining: mature B cells, lymphomas (even plasmacytoid lymphomas)
Micro images: plasma cells in Rosai-Dorfman disease
Micro images (AJSP subscribers): primary effusion lymphoma (figure C)
Micro images (Hum Path subscribers): primary effusion lymphoma (figure E)
Micro images (Mod Path subscribers): keratoacanthoma #1 (figure B), #2 (figure B), invasive squamous cell carcinoma
References: Mod Path 2002;15:45; AJSP 2002;26:1363
 

CD139

Positive staining (normal): B cells, monocytes, granulocytes, erythrocytes (weak), dendritic cells, glomeruli
Negative staining: T cells
 

CD140a

Aka alpha platelet derived growth factor receptor
 

CD140b

Aka beta platelet derived growth factor receptor
 

CD141

Aka thrombomodulin
75kD transmembrane glycoprotein and cofactor for the thrombin-mediated activation of protein C
Marker of mesotheliomas, endothelial cells and coagulation factor
Important fibrinolytic inhibitor, as it decreases the activation of plasminogen to plasmin
Critical for activation of protein C and initiation of the protein C anticoagulant pathway
Plasma CD141 levels are associated with endothelial damage
Interpretation: membranous staining pattern, often focal (cylasmic staining may be artifactual)
Uses:
Mesothelioma vs. lung adenocarcinoma: 64% sensitive, 95% specific for mesotheliomas, but must exclude vasculature; often membranous staining of periphery with isolated papilla; negative staining in sarcomatoid mesotheliomas; considered to have a “secondary” role as other markers are better, Hum Path 2002;33:953
Urothelial carcinomas (positive) vs. renal cell, prostate, endometrial or colonic carcinomas, AJSP 2001;25:1380
Squamous cell carcinomas (positive), AJCP 1998;110:385, AJSP 2003;27:150
Positive staining (normal): endothelial cells, megakaryocytes, keratinocytes, mesothelial cells, monocytes, neutrophils, platelets, smooth muscle cells, syncytiotrophoblasts, synovial lining cells, urothelium
Positive staining (tumors): mesothelioma (epithelioid), squamous cell carcinomas, trophoblastic tumors, urothelial carcinomas, vascular tumors (including angiosarcoma), synovial sarcoma (diffusely positive in 10%, AJSP 2001;25:610)
Negative staining: adenocarcinoma of colon, endometrium, kidney, lung (usually), prostate; sarcomatoid mesothelioma,
Micro images (AJSP subscribers): lung squamous cell carcinoma, lung adenocarcinoma, mesothelioma (figure 1B)
 

CD142

Aka coagulation Factor III, thromboplastin, tissue factor
Major initiator of clotting in normal hemostasis and many thrombotic diseases, via complex with factor VIIa
Also binds zymogen factor VII, the inactive precursor form; once bound, a variety of serine proteases rapidly activate factor VII to VIIa via limited proteolysis
Normally absent from all cells in direct contact with plasma
Positive staining (normal): epidermal keratinocytes, glomerular epithelial cells and various other epithelia, adventitial cells of blood vessels, astrocytes, myocardium, Schwann cells, stromal cells of liver, pancreas, spleen and thyroid
 

CD143

Aka angiotensin-converting enzyme, ACE, peptidyl dipeptidase A
Involved in metabolism of angiotensin II and bradykinin; also cleaves substance P and LH-RH
Patients with high activity have DD genotype, associated with MI, strokes, diabetic nephropathy
Necessary for spermatozoa to bind to egg and associated with better penetration of egg
Positive staining (normal): endothelial cells of small/medium arteries, lung capillary endothelium, proximal renal tubule brush borders, basal ganglia neuropil, granulosa cells, Leydig cells, variable on other cells
 

CD144

Endothelial-specific cadherin localized at intercellular junctions
Aka vascular endothelial-cadherin precursor, VE-cadherin, cadherin 5
Cadherins are cell adhesion proteins that preferentially interact with themselves in a homophilic manner in connecting cells, thus contributing to the sorting of heterogeneous cell types
Positive staining (normal): endothelial cells, brain
 

CDw145

No information available
 

CD146

Aka melanoma cell adhesion molecule (MEL-CAM), cell surface glycoprotein MUC18
May be a neural crest cell adhesion molecule during embryogenesis
Associated with tumor progression and the development of metastasis in human malignant melanoma
Sensitive but nonspecific marker of desmoplastic/spindle cell melanoma; use if suggestive histology, S100 positive, melanoma markers otherwise negative, AJSP 2001;25:58
Interpretation:
expression is membranous
Positive staining (normal): vascular smooth muscle, endothelium, intermediate trophoblast in exaggerated placental sites and placental site trophoblastic tumors (Hum Path 1999;30:687), subpopulation of T cells, endothelium, smooth muscle, Schwann cells
Positive staining (tumors): clear cell sarcoma (90%), leiomyosarcomas (almost all), melanoma (desmoplastic-84%, epithelioid melanomas-100%, advanced primary tumors and metastatic tumors), melanotic schwannoma (100%), MPNST (27%), neurofibroma (40%), prostatic adenocarcinoma and high grade PIN, squamous cell carcinomas (some), vascular sarcomas (almost all)
Negative staining: normal melanocytes, melanocytic nevi, cellular blue nevus, thin primary melanomas, placental site nodules (or focal), epithelioid trophoblastic tumors (or focal), cytotrophoblast, atypical fibroxanthoma
Micro images (AJSP subscribers): desmoplastic melanoma (figure 1D), clear cell sarcoma (figure 3C), melanotic schwannoma (figure 4C)
Reference: AJSP 2001;25:58
 

CD147

Aka neurothelin, extracellular matrix metalloproteinase inducer
Positive staining (normal): all leukocytes, red blood cells, platelets and endothelial cells
 

CD148

Aka HPTP-eta
May be involved in contact inhibition of cell growth
Positive staining (normal): granulocytes, monocytes, memory T cells, dendritic cells, platelets, fibroblasts, neurons, Kupffer cells
 

CDw149

Deleted (now designated CD47R) at the 7th HLDA Workshop
Reference: Tissue Antigens 2000;56:258
 

CD150

Aka signal lymphocyte activation molecule (SLAM)
Costimulatory molecule on B lymphocytes and dendritic cells
Positive staining (normal): thymocytes, CD45RO positive subpopulation of T cells, B cells, dendritic cells, endothelium
 

CD151

May modify integrin function or signaling
Positive staining (normal): endothelium, platelets, megakaryocytes, epithelium
 

CD152

Aka cytotoxic T lymphocyte-associated protein-4, CTLA4
Negative regulator of T cell activation
CTLA4 restriction fragment length polymorphisms are linked to various autoimmune disorders
Shares sequence homology with CD28; also shares ligands CD80 and CD86 with CD28
Positive staining (normal): activated but not resting T cells, activated B cells
References: 123890
 

CD153

Aka CD30 ligand
Enhances CD3-activated T lymphocyte proliferation
 

CD154

Aka CD40 ligand, CD40L, TNF-related activation protein (TRAP)
Regulates B cell function by engaging CD40
Defective gene prevents immunoglobulin class switch and is associated with hyper IgM syndrome, autoimmune hematologic disorders, disorganized nodal follicular architecture and PAS-positive plasmacytoid cells containing IgM, lymph nodes without germinal centers, shortened lifespan, often with gastrointestinal cancers (cholangiocarcinoma, hepatocellular carcinoma, and adenocarcinoma) and Cryptosporidium parvum infection
Positive staining (normal): T cells
 

CD155

Aka polio virus receptor
Involved in intercellular adhesion
Positive staining (normal): embryonic structures giving rise to spinal cord anterior horn motor neurons
 

CD156a

Aka ADAM8
May play a role in muscle differentiation
Possible role in neutrophilic extravasation
Positive staining (normal): neutrophils, monocytes
 

CD156b

Aka Tumor necrosis factor Alpha Converting Enzyme (TACE), ADAM17
Adhesion structure; releases soluble forms of tumor necrosis factor and transforming growth factor-alpha from cells
Positive staining (normal): all cells examined, with pro-domain removed
 

CD157

Aka Bone marrow STromal cell antigen 1 (BST1)
Facilitates pre-B-cell growth
33% homology to CD38
Overexpression may cause polyclonal B-cell abnormalities in rheumatoid arthritis
Positive staining (normal): granulocytes, monocytes, B cell progenitors, T cell subpopulations
 

CD158

Member of KIR (killer cell immunoglobulin like receptor) family, also called killer cell inhibitory receptors
Binding by HLA class I molecules causes inhibition of NK or T cell cytotoxic activity
Melanoma specific cytotoxic T lymphocytes may express KIR and regulate their ability to kill these tumors
Positive staining (normal): Natural killer cells (NK cells), some T cells
 

CD158a

Aka KIR2DL1/p58.1
Regulates NK cell mediated cytolytic activity
Includes two different molecules with inhibitory and activation effects, presumably encoded by different genes of the same family
Positive staining (normal): NK cell subset
 

CD158b

CD158b1 aka KIR2DL2/p58.2
CD158b2 aka KIR2DL3/p58.3
Regulates NK cell mediated cytolytic activity
Includes two different molecules with inhibitory and activation effects, presumably encoded by different genes of the same family
Positive staining (normal): NK cell subset, rare T cells
 
CD158c-KIR2DS6/KIRX
CD158d-KIR2DL4
CD158e1-KIR3DL1/p70
CD158e2-KIR3DS1/p70
CD158f-KIR2DL5
CD158g-KIR2DS5
CD158h-KIR2DS1/p50.1
CD158i-KIR2DS4/p50.3
CD158j-KIR2DS2/p50.2
CD158k-KIR3DL2/p140
CD158z-KIR3DL7/KIRC1
 

CD159a

Aka NKG2A, killer cell lectin-like receptor subfamily C member 1
Mediates signaling in the killing process by NK cells
Positive staining (normal): NK cells
 

CD160
 

Aka BY55

Expression tightly associated with peripheral blood NK cells and CD8+ T lymphocytes with cytolytic effector activity

Positive staining (normal): circulating NK (CD56 dim, CD116+) and T cells, spleen, small intestinal intraepithelial lymphocytes
 

CD161

Aka killer cell lectin-like receptor subfamily B, member 1
May mediate NK cell function
Positive staining (normal): NK cells, subset of CD4+ and CD8+ T cells, memory T cells, thymocytes (some)
 

CD162

Aka P-Selectin Glycoprotein Ligand 1, PSGL-1
Important in adhesive interactions between circulating leukocytes and platelets and endothelial cells
Mediates rolling on activated endothelium or activated platelets (which express P selectin / CD62P) and other leukocytes at inflammatory sites
Site of binding of human granulocyte ehrlichiosis bacteria
Positive staining (normal): myeloid cells, stimulated T cells
 

CD162R
 

Positive staining (normal): NK cells
 

CD163

Hemoglobin/haptoglobin scavenger receptor
Soluble form attenuates immune response
Positive staining (normal): monocytes/macrophages
 

CD164

Aka MUC-24, sialomucin
Mucin-like cell surface glycoprotein that facilitates adhesion of CD34+ cells; regulates hemopoietic cell proliferation


 

CD165

Involved in adhesion between thymocytes and thymic epithelial cells
Positive staining (normal): immature thymocytes, monocytes, platelets, CNS neurons, islet cells, Bowman’s capsule of kidney
Positive staining (tumors): many T-acute lymphoblastic leukemias (ALL)
 

CD166

Aka Activated Leukocyte Cell Adhesion Molecule (ALCAM)
Adhesion molecule, binds to CD6
Involved in neuronal neurite extension, embryonic hemopoiesis, embryonic angiogenesis
Positive staining (normal): neurons, activated T cells, activated monocytes, epithelium, fibroblasts
 

CD167a

Aka Discoidin Domain Receptor 1, DDR1
Has homologous region to the Dicytostelium discoideum protein discoidin I in extracellular domain
Tyrosine kinase receptor, may be important in cytoskeletal organization and the ability to align with other cells during aggregation
Receptor tyrosine kinases help cells communicate with their microenvironment and regulate cell growth, differentiation and metabolism.
Activated by collagen types I-V, VIII
May have a role in tumor invasion and metastasis
Positive staining (normal): epithelial cells (breast, kidney, lung, GI, brain)
Positive staining (tumors): carcinomas (various)
 

CD168

Aka Receptor for Hyaluronic Acid-Mediated Motility (RHAMM)
Binding to hyaluron stimulates ciliary beating
Also has role in cell signaling, migration and adhesion
Positive staining (normal): bronchial epithelium, CNS neurons
 

CD169

Aka sialoadhesin
Macrophage-restricted cellular interaction molecule that binds sialylated ligands
Highly expressed on macrophages in chronically inflamed tissues, such as rheumatoid synovium and atherosclerotic plaques
Positive staining (normal): macrophages (all sites but microglia)
Negative staining: microglia
 

CD170

Aka Sialic acid binding IG-like LECtin 5 (SIGLEC5)
May function in cell-cell interaction
Positive staining (normal): neutrophils
 

CD171

Aka L1
Adhesion molecule required for normal neurohistogenesis
Mutations cause CRASH (Corpus callosum hypoplasia/agenesis, Retardation, Aphasia, Spastic paraplegia/shuffling gait and Hydrocephalus due to stenosis of aqueduct of Sylvius), an X linked neurologic disorder
May mediate kidney branching morphogenesis, maintenance of lymph node architecture during immune response, co-stimulation of T-cell activation in vitro
Positive staining (normal): post-mitotic neurons, glia, epithelial cells (some), lymphoid cells (some), myeloid (some), monocytes
 

CD172a

Aka SIRP alpha
Adhesion structure
 
 

CD173

Aka blood group H2
Marker of early hemaoiesis
Positive staining (normal): CD34+ hemopoietic progenitor cells
Negative staining: mature lymphocytes
 

CD174

Aka Lewis Y antigen
Marker of early hemaoiesis
Positive staining (normal): CD34+ hemopoietic progenitor cells
Negative staining: mature lymphocytes
 

CD175

Aka Tn
Simple mucin-type carbohydrate antigen produced in the initial steps of mucin biosynthetic pathway, due to aberrant or incomplete glycosylation of mucins
 

CD175s

Aka Sialyl Tn (STN)
Carbohydrate associated with apomucins MUC1, MUC2; produced in the initial steps of mucin biosynthetic pathway
Presence associated with aggressive tumors
High pre-operative serum levels predict liver metastasis and poor prognosis after resection for gastric cancer
Definitive Phase III trial of STN vaccine in metastatic breast cancer patients began 2001
Positive staining (tumors): carcinomas
 

CD176

Aka Thomsen-Friedenreich (TF) oncofetal blood group antigen, galactose beta 1-3 N-acetylgalactosamine alpha
Occurs in colon cancer and colitis
 

CD177

Aka NB1 glycoprotein
Major immunogenic molecule of neutrophil membrane
Positive staining (normal): myeloid cells
 

CD178

Aka CD95 ligand, Fas ligand (FasL)
Important role in T cell mediated cytotoxicity; induces apoptosis in Fas-expressing target cells
Cells in immune privileged sites (testis, anterior chamber of eye, placenta) constitutively express FasL, which induces apoptosis in Fas-expressing infiltrating T cells, minimizing inflammatory responses that might damage important physiologic functions at these sites
May influence interaction of tumor cells with host immune system; theory is that FasL+ tumor cells induce apoptosis in infiltrating Fas+ mononuclear cells
Fas-FasL binding triggers apoptosis in lymphocytes
Mutations may be related to some cases of Systemic Lupus Erythematosis (SLE)
Processed by metalloproteases which cause shedding of extracellular portion into blood (sFas L)
Positive staining (normal): activated and cytotoxic T cells, testis, anterior chamber of eye, placenta; also Sertoli cells, neurons, thyroid epithelial cells
Positive staining (tumors): Reed-Sternberg cells of Hodgkin’s lymphoma (nodular sclerosis and mixed cellularity, AJSP 2001;25:388)
Micro images (Hum Path subscribers): benign tamoxifen-exposed postmenopausal endometrium
 

CD179a

Aka VpreB1
Associates non-covalently with CD179b to form surrogate light chain as component of preB cell receptor, which plays a critical role in early B cell differentiation
Positive staining (normal): preB cells
 

CD179b

Aka lambda-5
Associates non-covalently with CD179a to form surrogate light chain as component of preB cell receptor, which plays a critical role in early B cell differentiation
Mutations impair B cell development and cause agammaglobulinemia
Positive staining (normal): preB cells
 

CD180

Aka RP105
Regulates B cell recognition of lipopolysaccharide, a membrane constituent of gram-negative bacteria
Positive staining (normal): mantle zone and marginal zone B cells (strong), other B cells (weak/negative); peripheral blood monocytes, dendritic cells
 

CD181

No information available
 

CD182

No information available
 

CD183

Aka CXCR3

Receptor for some chemokines; binding of chemokines to CD183 induces integrin activation, cytoskeletal changes and chemotactic migration in inflammation-associated effector T cells
CD183+ T cells detected in inflamed tissues of patients with juvenile rheumatoid arthritis, multiple sclerosis, sarcoidosis, hepatitis C
Positive staining (normal): T cells in inflamed tissue, eosinophils, plasmacytoid dendritic cells, hemopoietic progenitors
Negative staining: naïve T cells in peripheral blood
 

CD184

Aka CXCR4, Stromal cell Derived Factor 1 (SDF1)
Receptor for the CXC chemokine SDF-1
Also major HIV/SIV co-receptor (with CCR5/CD195)
Involved in B cell development, myelopoiesis, cardiac ventricular septum formation, blood vessel formation in GI tract, cerebellar granular cell development
Positive staining (normal): all mature blood cells, blood progenitor cells, endothelial and epithelial cells, astrocytes, neurons
 

CD185

No information available
 

CD186

No information available
 

CD187

No information available
 

CD188

No information available
 

CD189

No information available
 

CD190

No information available
 

CD191

No information available
 

CD192

No information available
 

CD193

No information available
 

CD194

No information available
 

CD195

Aka CCR5
Macrophage surface receptor and attachment site for HIV and SIV, with CXCR4 (CD184); works with CD4
Receptor for CD8 chemokines RANTES, MIP 1-alpha and MIP 1-beta.
 

CD196

No information available
 

CDw197

Aka CCR7
 

CD198

No information available
 

CD199

No information available
 

CD200

Aka OX2
An immunoadhesin that may deliver immunosuppressive signals and regulate autoimmune disorders
Inhibitory for macrophage lineage cells
Positive staining (normal): follicular dendritic cells, thymocytes, B cells, T cells, neurons, kidney glomeruli, syncytiotrophoblast, endothelial cells
 

CD201

Binds protein C in a calcium-dependent manner
Aka Endothelial Protein C Receptor (EPC R), protein C receptor
Protein C is a vitamin K dependent enzyme with major role in coagulation of blood; activated when thrombin binds to thrombomodulin on endothelium.
Mutations in CD201 and thrombomodulin associated with late fetal loss; similar mutation associated with venous thromboembolism and myocardial infarction
Positive staining (normal): endothelial cells (not in liver and kidney)
 

CD202b

Aka Tie2 (Tyrosine kinase with Ig-like loops and Epidermal growth factor homology domains), aka Tek
Receptor tyrosine kinase at #9p21, binds to angiopoietin-1
May be earliest mammalian endothelial cell lineage marker
Involved in vein morphogenesis and communication between endothelial and smooth muscle cells for remodeling and repair of blood vessels
Defects associated with inherited venous malformations
Positive staining (normal): endothelial cells, hemopoietic cells
 

CD203c

Aka E-NPP3/PDNP3
Enzyme that catalyzes hydrolysis of oligonucleotides, nucleoside phosphates, and NAD
Positive staining (normal): prostate, uterus, basophils, mast cells, gliomas, myeloid cells
 

CD204

Aka macrophage scavenger receptor 1
Plays a role in endocytosis of macromolecules
Positive staining (normal): myeloid cells
 

CD205

Aka DEC205
Possible antigen-uptake receptor with a role in initiating immune response
Positive staining (normal): dendritic cells
 

CD206
Aka macrophage mannose receptor
Acts in phagocytosis and pinocytosis of mannose-containing solutes
Positive staining (normal): dendritic cells
 

CD207
Aka langerin (Langerhans cell specific c-type lectin)
Functions as endocytic receptor
Localized to Birbeck granules
Mannose binding to this protein may cause antigen internalization into Birbeck granules and access to a nonclassical antigen-processing pathway
Positive staining (normal): Langerhans cells (immature dendritic cells of epidermis and mucosa)
 

CD208
Dendritic cell LAMP (DC-Lamp)
Indicates dendritic cell maturation
Positive staining (normal): dendritic cells
 

CD209
Aka DC-Sign
Binds to HIV1 gp120
Mediates transient adhesion of dendritic cells with T cells
Positive staining (normal): dendritic cells
 

CDw210
Aka IL-10 receptor
Interleukin-10 (124092) produced by B cells, T helper cells, and monocyte/macrophages, exhibits diverse activities on different cell lines
IL10 inhibits macrophage activation by interferon-gamma
Positive staining (normal): monocytes, B and T cells, large granular lymphocytes, spleen, thymus, placenta, lung, liver
 

CD211
No information available
 

CD212
Aka IL-12 receptor
Interleukin-12 promotes cell-mediated immunity to intracellular pathogens by inducing type 1 helper T cell responses and interferon-gamma production.
Lack of IL12 associated with severe, idiopathic mycobacterial and Salmonella infections, mature granulomas
Positive staining (normal): T cells, NK cells
 

CD213a1
Aka IL-13 receptor, alpha 1
Binds IL-13 with low affinity
With IL-4r-alpha, can form a functional receptor for IL-13
Positive staining (normal): ubiquitous, B-cells, T-cells and endothelial cells, highest levels in heart, liver, skeletal muscle and ovary
 

CD213a2
Aka IL-13 receptor, alpha 2
Inhibits binding of interleukin-13 to the IL13 cell surface receptor
Positive staining (normal): placenta
 

CD214
No information available
 

CD215
No information available
 

CD216
No information available
 

CDw217
Aka IL 17 receptor
Cytokine that is induced in activated CD4+ T cells
IL17 induces stromal cells to produce proinflammatory and hemopoietic cytokines; enhances expression in fibroblasts of ICAM-1
 

CD218
No information available
 

CD219
No information available
 

CD220
Aka insulin receptor
 

CD221
Aka insulin-like growth factor 1 receptor
Mediates insulin stimulated DNA synthesis and IGF1 stimulated cell proliferation and differentiation
Often overexpressed in malignant tissue, where it functions as an anti-apoptotic agent by enhancing cell survival
 

CD222
Aka insulin-like growth factor 2 receptor, mannose 6 phosphate receptor
Also a receptor for lysosomal hydrolases (i.e. assists in sorting lysosomal enzymes from Golgi apparatus or extracellular space to lysosomes)
 

CD223
Aka Lymphocyte-Activation Gene 3 (LAG-3)
Homologous to CD4
Associates with MHC class II molecules on monocytes/dendritic cells, which are subsequently activated
May help activated CD4+ and CD8+ T cells to fully activate monocytes and dendritic cells, leading to optimized MHC class I and class II T cell responses
Positive staining (normal): activated T cells, activated NK cells
 

CD224
Aka gamma-glutamyltransferase
Gene at 22q11.1-q11.2
Catalyzes the transfer of the glutamyl moiety of glutathione to a variety of amino acids and dipeptide acceptors, which maintains a homeostatic balance regarding oxidative stress.
 

CD225
Aka Leu13, interferon-inducible transmembrane protein 1
Involved in relaying antiproliferative and homotypic adhesion signals
 

CD226
Aka DNAM-1, Platelet and T cell Activation antigen 1 (PTA1)
Mediates adhesion to an unknown ligand
T cell expression increased in some patients with autoimmune disease and viral infection
Positive staining (normal): NK cells, platelets, monocytes, subset of B and T cells
Negative staining: granulocytes, erythrocytes
 

CD227
Aka EMA, MUC1, episialin
Large cell surface mucin glycoprotein expressed by most glandular and ductal epithelial cells and some hemopoietic cells
Highly expressed by most adenocarcinomas, associated with poor prognosis, Hum Path 1995;26:432
Shed into the bloodstream of adenocarcinoma patients, used in commercial serum tumor marker assays (CA15-3)

Expressed by nearly all cases of Paget’s disease, can use to screen/confirm presence of Paget’s cells in epidermis, AJSP 2001;25:1469
Associated with invasion in pancreatic tumors, AJSP 2002;26:466
Positive staining (normal):
apical surface of almost all glandular and ductal epithelial cells including breast and pancreas, activated T cells, monocytes, some B cells, follicular dendritic cells, perineurial cells
Positive staining (tumors): adenocarcinoma (most), anaplastic large cell lymphoma, epithelioid sarcoma, meningioma, mesothelioma (some), myeloma, Paget’s disease, plasmacytoma
Negative staining: hepatocellular and adrenal carcinoma, germ cell tumor
Micro images: synovial sarcoma staining of glandular structures, urothelial carcinoma-high grade
References: J Leukoc Biol 2002;72:692
 

CD228
Aka melanotransferrin
Cell-surface glycoprotein found on melanoma cells, with sequence similarity and iron-binding properties of transferrin superfamily
 

CD229
Aka Lymphocyte antigen 9
May be involved in adhesion between T cells and accessory cells
 

CD230
Aka prion protein (“PRotein INfectious agent”)
Mutations associated with Gerstmann-Straussler disease, Creutzfeldt-Jakob disease (CJD), familial fatal insomnia, which are neurodegenerative conditions transmissible by inoculation or inherited as autosomal dominant disorders
Aberrant isoforms can act as an infectious agent in these disorders as well as in kuru and in scrapie in sheep
Replication (infectivity) occurs as abnormal protein with conformational change recruits cellular prion and converts it into infective form with same conformational change
Positive staining (normal): neurons (nonpathogenic isoform)
Reference: 176640
 

CD231
Aka T cell Acute Lymphoblastic Leukemia Antigen-1 (TALLA-1), TM4SF2, A15
Involved in X-linked mental retardation, Nat Genet 2000;24:167
Positive staining (normal):
brain neurons
Positive staining (tumors): T cell acute lymphoblastic leukemia, neuroblastoma cells
Negative staining: B cells, monocytes
 

CD232
Aka Virus Encoded Semaphoring Protein Receptor (VESP R)
May function as an immune modulator during virus infection.

CD233
Aka band 3
Erythrocyte membrane protein that functions as an anion (chloride/bicarbonate) exchanger and attachment site for cytoskeleton (where spectrin/actin bind to membrane lipid bilayer)
Truncated form of CD233 is expressed in kidney and involved in acid secretion
Mutations cause hereditary spherocytosis or distal renal tubular acidosis (due to defective acid secretion)
Other mutations cause novel blood group antigens which form the Diego blood group system
Southeast Asian ovalocytosis is due to heterozygous deletions, common where Plasmodium falciparum malaria is endemic, associated with abnormally rigid, stomatocytic erythrocytes, asymptomatic; children are protected against cerebral malaria
Positive staining (normal): erythrocyte plasma membrane (strong), basolateral membrane of a-intercalated cells of the distal tubules and collecting ducts of the kidney
Negative staining: all other cells
 

CD234
Aka Duffy blood group antigen (Fy glycoprotein); erythrocyte chemokine receptor, Duffy Antigen Receptor for Chemokines (DARC)
RBC receptor for Plasmodium vivax, a malarial parasite
Negativity associated with sickle cell trait, due to common protection against malaria provided by both traits African-Americans often Duffy negative and resistant to P. vivax malaria
Positive staining (normal): endothelial cells of post-capillary venules, Purkinje cells of cerebellum
 

CD235a

Glycophorins A and B are major sialoglycoproteins of the human erythrocyte membrane
Contains antigenic determinants for the MN blood group
Positive staining (normal): erythroid cells
 

CD235b

Glycophorins A and B are major sialoglycoproteins of the human erythrocyte membrane
Contains antigenic determinants for the MN blood group
Positive staining (normal): erythroid cells

CD235ab

Positive staining (normal): erythroid cells

CD236

Positive staining (normal): erythroid cells

CD236 R

Positive staining (normal): erythroid cells

CD237

CD238

Positive staining (normal): erythroid cells

CD239

May mediate cell-cell, cell-matrix adhesion, signal transduction
Positive staining (normal): erythroid cells
 

CD240 CE

Positive staining (normal): erythroid cells
 

CD240 D

Positive staining (normal): erythroid cells
 

CD240 DCE

Positive staining (normal): erythroid cells
 

CD241
Aka Rh50a, Rh antigen
Rhesus blood group-associated glycoprotein; plays role in transport of antigen to cell surface of red blood cells
Positive staining (normal): erythroid cells
 

CD242
Aka intercellular adhesion molecule 4 (ICAM-4), Landsteiner-Wiener blood group
Discovered with antibody raised in guinea pigs injected with the cells of rhesus monkeys, but Rh designation had already been taken

 

CD243
Aka MDR-1 (multidrug resistance to cancer), P glycoprotein
Member of large superfamily of highly conserved ATP binding cassette transport proteins
"Detoxifying agent" that pumps toxins out of cells, also transports steroid hormones
Prognostic importance: correlates with poor response to chemotherapy / shorter survival for osteosarcoma
Positive staining (normal): adrenal cortex, biliary canaliculi, blood-brain endothelium, blood-testicle endothelium, placenta, GI endothelium, proximal renal tubules, some bone marrow stem cells
 

CD244
Aka 2B4
NK cell surface receptor; regulates NK and T cell function
 

CD245

Aka p220/240
 

CD246
Anaplastic lymphoma kinase gene at 2p23; Also called CD246
Membrane spanning tyrosine kinase receptor, member of insulin receptor family
Ligand is growth factor pleiotrophin
3' end contains catalytic domain of tyrosine kinase
t(2;5) associated with T cell anaplastic lymphoma via fusion of ALK and nucleophosmin protein
Has important role in brain development
ALK+ primary anaplastic large cell lymphomas have favorable prognostic significance
ALK- cases of primary anaplastic large cell lymphoma are associated with trisomy 2 (Mod Path 2005;18:235)
Positive staining (normal): normal small intestine, T cells; weakly positive in brain, colon, prostate
Positive staining (tumors): T or null cell anaplastic lymphomas (some), inflammatory myofibroblastic tumor (AJSP 2001;25:1364, AJSP 2001;25:761)
Negative staining: fibromatosis, GIST, nodular fasciitis, normal lymphoid tissue
Micro images: anaplastic lymphoma [(c) Canadian Assoc of Pathologists]
Micro images (Hum Path subscribers): anaplastic large cell lymphoma #1, #2
 

CD247
Aka zeta chain, T cell receptor zeta
Forms T cell-CD3 receptor complex, together with TCR alpha/beta and gamma/delta heterodimers, CD3-gamma, delta and epsilon
Couples antigen recognition to several intracellular signal-transduction pathways; low expression of the antigen results in impaired immune response.
Positive staining (normal):  T cells