CD Markers - CD100 to CD400

(a) regulates axonal growth cone guidance in the developing CNS through its receptor plexin-B1, which may be related to its expression in invading islands of transformed epithelial cells (but not normal and noninvasive dysplastic epithelium, Proc Natl Acad Sci USA 2006;103:9017)

(b) evokes angiogenic responses from endothelial cells (Blood 2005;105:4321)

(d) after vascular injury, platelet associated CD100 binds to CD100 receptors on nearby platelets to promote thrombus formation (Proc Natl Acad Sci USA 2007;104:1621)

(e) increases CD45 induced T cell adhesion

(f) down regulates B cell expression of CD23

Expression may have prognostic value in soft tissue sarcoma (Cancer 2007;110:164)

Uses: no significant clinical use by pathologists

Positive staining (normal): most hematopoietic cells including platelets, increased expression after T cell activation

Negative staining: immature bone marrow cells

Micro images: head and neck squamous cell carcinoma

References: OMIM 601866, Wikipedia (semaphorins)

CD101

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Also called immunoglobulin superfamily member 2 (IGSF2), V7

Inhibits T cell activation induced by CD3, by (a) inhibiting IL-2RA expression on activated T cells and IL2 secretion (J Immunol 1998;161:209), (b) inducing IL10 production (Eur J Immunol 2000;30:3132)

Uses: no significant clinical use by pathologists

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

Positive staining (disease): CD4+ CD56+ blastic tumor cells (J Invest Dermatol 2005;124:668), Langerhans cell histiocytosis (Histopathology 2000;36:229)

Micro images: CD4+ CD56+ blastic tumor cells

References: OMIM 604516, J Immunol 1998;161:2780

CD102

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Also called ICAM-2

Binds the leukocyte integrins LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18)

Provides costimulatory signal in immune response; important in lymphocyte recirculation (J Immunol 2003;171:2588)

Endothelial ICAM-2 mediates angiogenesis (Blood 2005;106:1636)

Elevated serum levels in (a) hemorrhagic fever with renal syndrome (Viral Immunol 2006;19:565) and (b) idiopathic pulmonary fibrosis (Inflammation 2004;28:359)

Uses: no significant clinical use by pathologists

Positive staining (normal): resting lymphocytes, monocytes, platelets, vascular endothelial cells

Positive staining (disease): some lymphomas

Negative staining: neutrophils

References: OMIM 146630

CD103

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Also called human mucosal lymphocyte antigen 1, integrin alpha E beta 7

CD103+ tumor infiltrating lymphocytes have a cytotoxic antitumor effect (J Exp Med 2007;204:559), may play a role in renal allograft rejection (Am J Transplant 2004;4:1026, J Exp Med 2002;196:873)

Uses: marker for hairy cell leukemia, intraepithelial lymphocytes (normal or tumor)

Positive staining (normal): intraepithelial T lymphocytes (90% in GI, tonsil-J Immunol 2005;175:4355, 30% in lung-Clin Exp Immunol 2007;149:162), lamina propria T lymphocytes in the intestine (50%), dendritic cells in gut (J Exp Med 2005;202:1051), rare peripheral blood lymphocytes

Positive staining (disease): hairy cell leukemia (usually, AJCP 2006;125:251), enteropathy-associated T cell lymphoma, splenic marginal zone lymphoma (some)

Flow cytometry images: hairy cell leukemia variant often expresses CD103 but not CD25 #1; #2 (fig C)

References: OMIM 604682

CD104

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Also called integrin beta 4 chain

Tends to associate with alpha 6 subunit (CD49f)

Adhesion receptor (for laminins) in normal epithelia that plays a critical role in structure of hemidesmosomes; associated with intermediate filaments

May contribute to tumor progression (Cancer Metastasis Rev 2005;24:413) via VEGF stimulation (J Cell Biol 2002;158:165)

Overexpressed in pancreatic adenocarcinoma (J Histochem Cytochem 2005;53:799)

Mutations are associated with epidermolysis bullosa with pyloric atresia (Exp Dermatol 2004;13:61)

Uses: no significant clinical use by pathologists

Positive staining (normal): epithelium, thymocytes, Schwann cells

Positive staining (disease): carcinomas (some)

Micro images: normal pancreas and adenocarcinoma

References: OMIM 147557

CD105

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Also called endoglin

Regulatory component of TGF-beta receptor complex; mediates cellular response to TGF-beta 1

Mutations cause Hereditary Hemorrhagic Telangiectasia type I (Am J Hum Genet 1997;61:68)

Required for hemangioblast and early hematopoietic development (Development 2007;134:3041)

Uses: specific and sensitive marker for tumor angiogenesis (better than CD31)

Poor prognostic factor - increased microvessel staining: acute lymphoblastic leukemia in children (Leuk Res 2007 Jun 15; [Epub ahead of print]), breast carcinoma (AJCP 2003;119:374, including node negative-Hum Path 2004;35:176), chronic idiopathic myelofibrosis (Mod Path 2004;17:1513), colorectal carcinoma (Mod Path 2004;17:197), endometrial carcinoma (Gynecol Oncol 2006;103:1007), esophageal adenocarcinoma (Hum Path 2006;37:861), gastric carcinoma (Hum Path 2006;37:861), hepatocellular carcinoma (BMC Cancer 2006;6:110), meningioma (Acta Neuropathol (Berl) 2007;114:147), ovarian carcinoma (Int J Gynecol Cancer 2006;16:1789), primary CNS lymphoma (J Neurooncol 2007;82:249), prostate adenocarcinoma (AJCP 2007;127:572), squamous cell carcinoma of head and neck (Virchows Arch 2006;448:768), including tongue (Laryngoscope 2006;116:1175)

Poor prognostic factor - other: serum endoglin is associated with intrauterine growth retardation during pregnancy (J Clin Endocrinol Metab 2007;92:2831), preeclampsia (N Engl J Med 2006;355:992, Nat Med 2006;12:642), diabetic retinopathy (J Cell Mol Med 2005;9:692)

Tissue endoglin is associated with progressive hepatic fibrosis in chronic HCV infection (J Viral Hepat 2006;13:625) and aortic atherosclerosis (J Atheroscler Thromb 2006;13:82)

Positive staining (normal): activated monocytes, erythroid precursors in marrow; syncytiotrophoblast, cytotrophoblast in first trimester (transient expression)

Positive staining (disease): endometriosis (Reprod Biol 2005;5:51), tumor microvessels (Rom J Morphol Embryol 2007;48:41)

Negative staining: normal endothelial cells (or weak)

Micro images: chronic idiopathic myelofibrosis (fig c, e, f); endometriosis (fig 3-5); liver-normal liver (fig 4); hepatocellular carcinoma #1; #2 and normal liver; lung-non small cell carcinoma (fig D)

References: J Transl Med 2004;2:18

CD106

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Also called VCAM-1 (vascular cell adhesion molecule 1); alpha 4 beta 1 ligand

Interacts with beta 1 integrin VLA4

Adhesion molecular in activated endothelium; plays a role in migration of white blood cells (J Exp Med 2006;203:2763)

May mediate endothelial progenitor cell recruitment to rheumatoid arthritis synovium (Arthritis Rheum 2007;56:1817); associated with type II rheumatic disease (Cell Mol Biol (Noisy-le-grand) 2002;48 Online Pub:OL243)

Important in initiation of atherosclerosis (J Clin Invest 2001;107:1255)

Renal cell carcinoma may exploit VCAM-1 overexpression for immune system escape (Cancer Res 2007;67:6003); on the other hand, down regulation in breast cancer is associated with nodal metastases (Pathol Oncol Res 2002;8:125)

Increased expression: in placentas of women with pregnancy induced hypertension complicated by intrauterine growth retardation (Di Yi Jun Yi Da Xue Xue Bao 2002;22:1022)

Increased plasma levels: associated with: breast cancer [high stage] with circulating cancer cells (Neoplasma 2006;53:538), cancer (general)-early stage or preclinical (Eur J Cancer 2005;41:2355), dengue virus infection severity (J Med Virol 2004;72:445), diabetes with poor control (high HbA1c-Diabetes Care 2007;30:159 or arteriosclerosis obliterans-Clin Chim Acta 2007;377:198), endometriosis-advanced (J Soc Gynecol Investig 2002;9:98), sickle cell trait in athletes (J Appl Physiol 2007;102:169)

Uses: marker of endothelial damage (Endothelium 2006;13:335)

Positives staining (normal): activated endothelial cells, lymphocytes, monocytes, neural cells, hematopoietic cells

Positive staining (disease): renal cell carcinoma

Micro images: squamous cell carcinoma-well differentiated

References: OMIM 192225

CD107a

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Also called lysosome associated membrane protein 1 (LAMP-1)

Note: DC-LAMP is CD208

Functions:

(a) surface antigen transiently present on cell surface of CD8+ T cells after release of cytolytic granules (J Immunol Methods 2003;281:65)

(b) basophil activation antigen (Cell Res 2005;15:325)

(d) critical to phagosomes acquiring microbicidal capabilities (Cell Microbiol 2007 May 15; [Epub ahead of print])

(e) ligand to E-selectin mediated cell adhesion

Uses: defective CD107a surface expression discriminates between genetic subtypes of familial hemophagocytic lymphohistiocytosis (Blood 2006;108:2316); used to measure degranulation in CD8+ T cells by flow cytometry (Nat Med 2003;9:1377) and NK cell activity / cytolytic capacity (J Immunol Methods 2004;294:15)

Positive staining (normal): primarily endosome-lysosome membranes, 1-2% on plasma membrane; degranulated platelets (Blood Coagul Fibrinolysis 2003;14:249-53), activated neutrophils, T cells, endothelium

Diagrams: structure

References: OMIM 153330

CD107b

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Also called lysosome associated membrane protein 2 (LAMP-2)

X linked

Major constituent of lysosomal membranes (also LAMP-1)

Functions:

(a) mutations cause Danon disease, a lysosomal glycogen storage disease with cardiomyopathy in adult women and men before age 20 years (N Engl J Med 2005;352:362, Circulation 2005;112:1612), Wolff-Parkinson-White syndrome, myopathy, variable mental retardation and retinopathy (Arch Ophthalmol 2007;125:231); skeletal and cardiac muscle cells have intracytoplasmic vacuoles containing glycogen and autophagic material

(b) levels decrease with age (J Cell Sci 2007;120:782)

(c) binding of substrates to LAMP-2 is limiting step in chaperone-mediated autophagy, a selective mechanism for the degradation of soluble cytosolic proteins in lysosomes (EMBO J 2006;25:3921)

(d) may be involved in infection induced involution of thymus via autophagy (Acta Biol Hung 2006;57:315)

(e) facilitates MHC class II presentation of cytoplasmic antigens (Immunity 2005;22:571)

(f) basophil activation antigen (Cytometry A 2004;61:62)

Uses: help differentiate cardiomyopathy due to Danon disease (LAMP-2 negative) from other causes (LAMP-2+, Intern Med 2007;46:757)

Positive staining (normal): lysosome membranes of various tissues, platelets (Thromb Haemost 1996;75:623)

Negative staining: cardiac and skeletal muscle in Danon disease (Neuromuscul Disord 2003;13:708)

Diagrams: structure

Micro images: loss of LAMP-2 in hypertrophic cardiomyopathy patient #1 with Danon disease (fig A, B); #2 (fig A); #3 (loss of staining in muscle and heart); LAMP2+ cardiac myocytes in non Danon disease cardiomyopathy (fig 1g)

References: OMIM 309060

CD108

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Also called semaphorin 7A (SEMA7A) or John-Milton-Hagen (JMH) human blood group antigen

A semaphorin (Wikipedia)

Receptors are plexin C1 and beta1 integrins

Functions:

(a) genetic variations may play a role in decreased bone mineral density and risk of vertebral fracture (J Hum Genet 2006;51:112)

(b) extremely potent monocyte activator; stimulates chemotaxis and cytokine production (Scand J Immunol 2002;56:270)

(d) negative regulator of T cell responses (Immunity 2006;24:591)

(e) expression is correlated with the establishment of dentin-pulp complex terminal innervation (Matrix Biol 2005;24:232)

Positive staining (normal): erythrocytes, activated lymphocytes, odontoblasts, monocytes, keratinocytes, fibroblasts

References: OMIM 607961

CD109

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Also called Platelet activation factor

Glycosylphosphatidylinositol-anchored cell surface protein

Carries the biallelic platelet-specific Gov antigen system; alloantibodies to HPA-15 residing on CD109 are implicated in refractoriness to platelet transfusion, fetal/neonatal alloimmune thrombocytopenia and posttransfusion purpura (Blood 2002;99:1692)

Positive staining (normal): activation antigen for platelets and T cells; subset of hematopoietic stem and progenitor cells (Exp Hematol 1999;27:1282); myoepithelial cells (breast, prostate [basal cells] salivary and lacrimal glands, Pathol Int 2007;57:245); widely expressed in other tissues

Negative staining: invasive ductal carcinoma (breast), prostate adenocarcinoma

References: OMIM 608859

CD110

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Also called thrombopoietin receptor (TPO-R), myeloproliferative leukemia virus oncogene (MPL)

Binding to thrombopoietin induces megakaryocyte proliferation and differentiation and prevents apoptosis

Mutations present in some patients with congenital amegakaryocytic thrombocytopenia, characterized by severe congenital thrombocytopenia with no megakaryocytes in the bone marrow (Hum Mutat 2006;27:296)

MPL mutations in myelofibrosis patients are associated with more severe anemia (Br J Haematol 2007;137:244)

Thrombopoietin receptor agonists may be useful for treating thrombocytopenia (Blood 2007;109:4739)

Uses: differentiate essential thrombocythemia (variable but weak/negative staining) from reactive thrombocytosis (positive staining, Blood 2002;99:4131)

Positive staining (normal): hematopoietic stem cells and progenitor cells (J Transl Med 2006;4:9), megakaryocytes and progenitors, platelets

Diagrams: protein and site of various mutations

References: OMIM 159530, EntrezGene

CD111

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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

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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

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Also called nectin-3, poliovirus receptor-related protein 3 precursor

CD114

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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

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Aka c-fms, receptor for macrophage colony stimulating factor, CSF-1R

Localized on cytoplasmic 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

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GM-CSF receptor alpha chain

Primary binding subunit of GM-CSF receptor

Positive staining (normal): monocytes, neutrophils, eosinophils, fibroblasts, endothelial cells, dendritic cells

CD117

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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, hematopoietic 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

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 cytoplasmic staining, like the positive control

Positive staining (normal): interstitial cells of Cajal, hematopoietic 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 cytoplasmic 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: GIST vs. solitary fibrous tumor; malignant stromal tumor of gallbladder (figure 4); GIST (figures G, H); interstitial cells of Cajal in patient with multiple GIST tumors

References: Archives 2002;126:1189, AJSP 2002;26:486

CD118

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Reserved for interferon alpha / gamma receptor

CDw119

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Interferon gamma receptor

Positive staining (normal): macrophages, B cells

CD120a

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Aka TNFR1, receptor for tumor necrosis factor alpha and beta, type I

Receptor binding to ligand causes apoptosis

CD120b

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

CD121a

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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

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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

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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

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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

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Aka Interleukin 4 receptor

Receptor subunit for Interleukin-4 and 13

Positive staining (normal): mature B cells, T cells; hematopoietic precursors; fibroblasts, endothelial cells

CDw125

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Aka Interleukin 5 receptor alpha subunit

Therapeutic target of eosinophilic inflammation involved in bronchial asthma

Positive staining (normal): eosinophils, activated B cells, basophils

CD126

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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

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Aka Interleukin 7 receptor

Positive staining (normal): B cell precursors, most T cells, monocytes

CDw128a

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See CD181

CDw128b

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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

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Reserved for Interleukin 9 receptor

CD130

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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

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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

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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

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Aka prominin-like 1, AC 133

Alternative to CD34 in selecting hematopoietic stem and progenitor cells for transplantation studies

Localized to microvilli and other plasma membrane protrusions

Positive staining (normal): CD34 bright hematopoietic 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

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

CD135

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Aka FMS-like tyrosine kinase 3, flt3

Growth factor receptor for early hematopoietic progenitors

Positive staining (normal): multipotential, myelomonocytic, and primitive B cell progenitors

Positive staining (tumors): most AML, ALL and CML

CDw136

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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

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Costimulator of T cell proliferation

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

CD138

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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, plasmablastic lymphoma (strong), primary effusion lymphoma, pyothorax associated lymphoma

Negative staining: mature B cells, other lymphomas (even plasmacytoid lymphomas)

Micro images: keratoacanthoma #1 (figure B); #2 (figure B); invasive squamous cell carcinoma

References: Mod Path 2002;15:45; AJSP 2002;26:1363

CD139

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

Negative staining: T cells

CD140a

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Aka alpha platelet derived growth factor receptor

CD140b

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Aka beta platelet derived growth factor receptor

CD141

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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 (cytoplasmic 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,

CD142

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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

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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

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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

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May be expressed by endothelial cells

No other information available

CD146

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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

Reference: AJSP 2001;25:58

CD147

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Aka neurothelin, extracellular matrix metalloproteinase inducer

Positive staining (normal): all leukocytes, red blood cells, platelets and endothelial cells

CD148

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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

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Deleted (now designated CD47R) at the 7th HLDA Workshop

Reference: Tissue Antigens 2000;56:258

CD150

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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

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May modify integrin function or signaling

Positive staining (normal): endothelium, platelets, megakaryocytes, epithelium

CD152

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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

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Aka CD30 ligand

Enhances CD3-activated T lymphocyte proliferation

CD154

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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

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Aka polio virus receptor

Involved in intercellular adhesion

Positive staining (normal): embryonic structures giving rise to spinal cord anterior horn motor neurons

CD156a

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Aka ADAM8

May play a role in muscle differentiation

Possible role in neutrophilic extravasation

Positive staining (normal): neutrophils, monocytes

CD156b

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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

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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

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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

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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

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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

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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

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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

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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

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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

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Aka PEN5

Positive staining (normal): NK cells

CD163

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Hemoglobin/haptoglobin scavenger receptor

Soluble form attenuates immune response

Positive staining (normal): monocytes/macrophages

Positive staining (disease): histiocytic sarcoma (Diagn Pathol 2007;2:7)

Micro images courtesy of Drs. Charles J. Sailey, Borislav A. Alexiev and John C. Papadimitriou, Maryland (USA): histiocytic sarcoma

CD164

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Aka MUC-24, sialomucin

Mucin-like cell surface glycoprotein that facilitates adhesion of CD34+ cells; regulates hematopoietic cell proliferation

Positive staining (normal): small and large bowel epithelia; lung, thyroid epithelia

Positive staining (tumors): colorectal carcinoma, pancreatic adenocarcinoma

CD165

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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

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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

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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

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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

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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

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Aka Sialic acid binding IG-like LECtin 5 (SIGLEC5)

May function in cell-cell interaction

Positive staining (normal): neutrophils

CD171

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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

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Aka SIRP alpha

Adhesion structure

CD173

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Aka blood group H2

Marker of early hematopoiesis

Positive staining (normal): CD34+ hematopoietic progenitor cells

Negative staining: mature lymphocytes

CD174

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Aka Lewis Y antigen

Marker of early hematopoiesis

Positive staining (normal): CD34+ hematopoietic progenitor cells

Negative staining: mature lymphocytes

CD175

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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

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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

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Aka Thomsen-Friedenreich (TF) oncofetal blood group antigen, galactose beta 1-3 N-acetylgalactosamine alpha

Occurs in colon cancer and colitis

CD177

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Aka NB1 glycoprotein

Major immunogenic molecule of neutrophil membrane

Positive staining (normal): myeloid cells

CD178

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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)

CD179a

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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

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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

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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

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Also called CXCR1, IL8Ralpha; previously called CDw128A

Chemokine receptor, powerful neutrophil chemotactic factor

Positive staining (normal): neutrophils, basophils, T cell subset, monocytes, keratinocytes

Positive staining (disease): T cells in allergic rhinitis (J Immunol 2004;172:268)

CD182

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No information available

CD183

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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, hematopoietic progenitors

Negative staining: naïve T cells in peripheral blood

CD184

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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

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No information available

CD186

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No information available

CD187

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No information available

CD188

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No information available

CD189

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No information available

CD190

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No information available

CD191

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No information available

CD192

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No information available

CD193

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No information available

CD194

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No information available

CD195

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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

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No information available

CDw197

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Aka CCR7

CD198

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No information available

CD199

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No information available

CD200

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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

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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

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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, hematopoietic cells

CD203c

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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

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Aka macrophage scavenger receptor 1

Plays a role in endocytosis of macromolecules

Positive staining (normal): myeloid cells

CD205

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Aka DEC205

Possible antigen-uptake receptor with a role in initiating immune response

Positive staining (normal): dendritic cells

CD206

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Aka macrophage mannose receptor

Acts in phagocytosis and pinocytosis of mannose-containing solutes

Positive staining (normal): dendritic cells

CD207

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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

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Dendritic cell LAMP (DC-Lamp)

Indicates dendritic cell maturation

Positive staining (normal): dendritic cells

CD209

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Aka DC-Sign

Binds to HIV1 gp120

Mediates transient adhesion of dendritic cells with T cells

Positive staining (normal): dendritic cells

CDw210

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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

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No information available

CD212

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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

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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

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Aka IL-13 receptor, alpha 2

Inhibits binding of interleukin-13 to the IL13 cell surface receptor

Positive staining (normal): placenta

CD214

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No information available

CD215

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No information available

CD216

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No information available

CDw217

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Aka IL 17 receptor

Cytokine that is induced in activated CD4+ T cells

IL17 induces stromal cells to produce proinflammatory and hematopoietic cytokines; enhances expression in fibroblasts of ICAM-1

CD218

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No information available

CD219

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No information available

CD220

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Aka insulin receptor

CD221

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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

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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

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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

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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

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Aka Leu13, interferon-inducible transmembrane protein 1

Involved in relaying antiproliferative and homotypic adhesion signals

CD226

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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

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Aka EMA, MUC1, episialin

Large cell surface mucin glycoprotein expressed by most glandular and ductal epithelial cells and some hematopoietic 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: urothelial carcinoma-high grade

References: J Leukoc Biol 2002;72:692

CD228

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Aka melanotransferrin

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

CD229

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Aka Lymphocyte antigen 9

May be involved in adhesion between T cells and accessory cells

CD230

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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

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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

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Aka Virus Encoded Semaphoring Protein Receptor (VESP R)

May function as an immune modulator during virus infection.

CD233

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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

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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

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Aka Glycophorin A

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

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Aka Glycophorin B

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

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Aka Glycophorin A/B crossreactive antibodies

Positive staining (normal): erythroid cells

CD236

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Aka Glycophorin C/D

Positive staining (normal): erythroid cells

CD236 R

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Aka Glycophorin C

Regulates mechanical stability of red cells

Mutations cause Gerbich and Yus blood group phenotypes

Positive staining (normal): erythroid cells

CD237

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No information available

CD238

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Aka Kell blood group antigen

Positive staining (normal): erythroid cells

CD239

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Aka Lutheran blood group antigen; B-CAM

May mediate cell-cell, cell-matrix adhesion, signal transduction

Positive staining (normal): erythroid cells

CD240 CE

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Also called RH 30 CE, Rh blood group Cc and Ee blood group antigens; encodes RhC and RhE antigens on a single polypeptide

On #1p36.11 adjacent to RH D gene

Rh (rhesus) blood group system is second most clinically significant blood group after ABO; is most polymorphic blood group, with variations due to deletions, gene conversions, and missense mutations

Rh antigens are carried by an oligomer of two major erythroid specific polypeptides, the Rh (D and CcEe) proteins and the RhAG glycoprotein; Rh proteins form a core complex critical to structure of erythrocyte membrane (Blood Rev 2006;20:93); may play a role in ammonia transport (J Biol Chem 2002;277:12499, but see Transfus Clin Biol 2006;13:132)

Discrepant or doubtful serologic results can be resolved by PCR-SSP technique (Transfusion 2007;47:54S)

Rarely causes hemolytic disease of newborn (Transfus Med 2000;10:305)

Uses: blood typing

Positive staining (normal): erythroid cells

References: Blood Group Antigen Gene Mutation Database, Blood 2000;95:375, OMIM 111700

CD240 D

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Also called RH30 D, Rh blood group D blood group antigen; is major antigen of the Rh system

On #1p36.11 adjacent to RHCE gene

Rh (rhesus) blood group system is second most clinically significant blood group after ABO; is most polymorphic blood group, with variations due to deletions, gene conversions, and missense mutations

Weak D, formerly called D(u), occurs in 0.2 to 1% of whites; exhibits reduced expression of D antigen (Blood 1999;93:385); should not be labeled as Rh negative (Curr Opin Hematol 2006;13:476)

Individuals are classified as Rh positive or negative based on presence or absence of highly immunogenic D antigen on red cell surface

May have arisen historically by duplication of RHCE gene (Blood 2002;99:2272)

Discrepant or doubtful serologic results can be resolved by PCR-SSP technique (Transfusion 2007;47:54S)

Hemolytic disease of fetus and newborn: usually due to Rh negative woman whose partner is Rh+ or heterozygous and fetus is Rh+; woman has preexisting anti-RhD antibodies that cross placenta and harm fetus (Immunohematol 2006;22:188)

Can use maternal plasma in alloimmunized pregnancies to determine fetal RhD status (Fetal Diagn Ther 2006;21:404), or for RHD and RHCE genotyping (Prenat Diagn 2005;25:1079); genotyping from amniotic fluid or chorionic villi sampling was performed in past, but is more invasive (N Engl J Med 1998;339:1734, Clin Exp Med 2002;2:77)

Rh positive mothers may rarely (0.15%) develop new antibodies (other than anti-RHD) in third trimester, but no clinical significance (J Matern Fetal Neonatal Med 2007;20:59)

Having Rh negative mother may be risk factor for autistic children, due to use of mercury containing Rho-immune globulin (J Matern Fetal Neonatal Med 2007;20:385)

Uses: blood typing

Positive staining (normal): erythroid cells

References: Blood Group Antigen Gene Mutation Database, OMIM 111680, Wikipedia, eMedicine (Rh incompatibility)

CD240 DCE

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Rh30D/CE crossreactive monoclonal antibodies

Uses: blood typing

Positive staining (normal): erythroid cells of normal Rh types

Negative staining: Rh null erythrocytes

References: Washington State University

CD241

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Also called RH50 glycoprotein, RHAG, Rhesus blood group associated glycoprotein

Located at #6p21.1-p11

Is a strictly required posttranscriptional factor regulating Rh membrane expression (Blood 2002;100:1038)

Also appears to be an ammonium transporter (Proc Natl Acad Sci USA 2004;101:17222) and a CO2 channel (FASEB J 2007 Aug 21; [Epub ahead of print])

Defects cause Rh-null phenotype (OMIM 268150), associated with a chronic hemolytic anemia and spherostomatocytosis (J Biol Chem 1998;273:2207)

Uses: blood typing

Positive staining (normal): erythroid cells

References: OMIM 180297

CD242

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Also called intercellular adhesion molecule 4 (ICAM-4), Landsteiner-Wiener (LW) blood group protein

Discovered with antibody raised in guinea pigs injected with the cells of rhesus monkeys, but Rh designation had already been taken

Binds to CD11a/CD18, CD11b/CD18 and CD11c/CD18 (Blood 2007;109:802)

May be critical in erythroblastic island formation, where erythroid progenitors differentiate (Blood 2006;108:2064)

May be ligand for platelet-activated alpha IIb beta 3 integrin (J Biol Chem 2003;278:4892)

In sickle cell disease, contributes to red cell-endothelial cell adhesion and vasoocclusion (Transfus Clin Biol 2006;13:44)

Uses: no significant clinical use by pathologists

Positive staining (normal): erythroid cells

References: Blood Group Antigen Gene Mutation Database, OMIM 111250

CD243

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Also called MDR-1 gene (multidrug resistance to cancer), P glycoprotein 170 (molecular weight is 170K), ABCB1, P-binding cassette subfamily B member 1

Member of large superfamily of highly conserved ATP binding cassette transport proteins

"Detoxifying agent" that pumps toxins / drugs out of cells, also transports steroid hormones and transports substances across blood-brain barrier

Regulated by Y-box binding protein 1 (Clin Cancer Res 1998;4:2273)

May regulate cholesterol trafficking in cells (Proc Natl Acad Sci USA 2002;99:10347)

Levels reduced in inflamed intestinal epithelium of patients with GI disorders (Inflamm Bowel Dis 2007;13:710)

Specific polymorphisms affect gene expression and mRNA processing (AAPS J 2006;8:E515)

Specific polymorphism associations: ulcerative colitis (Hum Mol Genet 2006;15:797), Parkinson’s disease-reduced risk (Arch Neurol 2005;62:460); response to chemotherapy in small cell lung cancer (Jpn J Clin Oncol 2006;36:137)

MDR1 expression is poor prognostic factor in these malignancies: acute lymphoblastic leukemia - childhood (Oncol Rep 2004;12:1201) and adult types (Blood 2002;100:974), acute myelogenous leukemia-CD34 related coexpression of MDR1 and BCRP in patients age 60+ years (Ann Hematol 2007;86:329), acute promyelocytic leukemia in relapse (Haematologica 2002;87:1109), hepatocellular carcinoma-response to chemotherapy (World J Gastroenterol 2006;12:868), HIV related non-Hodgkin’s lymphoma (Pathol Res Pract 2007;203:1), lung and ovarian carcinoma (J Natl Cancer Inst 1992;84:1486), melanoma of uvea (Hum Path 1998;29:594), nasopharyngeal carcinoma (Hum Path 2001;32:1240), neuroblastoma (N Engl J Med 1991;325:1608), osteosarcoma (Int J Oncol 2006;29:1459), renal cell carcinoma (BMC Cancer 2006;6:293), soft tissue carcinoma-all ages (Hum Path 2005;36:994) and in children (J Clin Oncol 1990;8:689), Wilm’s tumor-staining of endothelial cells (AJCP 2002;117:484)

Uses: prognostic value in malignancies (see above)

Positive staining (normal): adrenal cortex (Acta Pathol Jpn 1990;40:545), brain endothelium (Exp Biol Med (Maywood) 2005;230:118), bronchi (Eur Respir J 1997;10:1837), duodenum-lateral and apical surfaces (Drug Metab Dispos 2005;33:1603), heart-vascular endothelium (J Histochem Cytochem 2002;50:1351), kidney-proximal tubules (Nephron 1997;77:284), liver-bile canaliculi (Arch Otolaryngol Head Neck Surg 1993;119:753), lung (J Clin Pathol 2002;55:332), lung-type I alveolar epithelium (J Pharmacol Exp Ther 2003;304:441), lymphocytes-CD4+ (Blood 1992;80:2735), placenta, retina (Mol Vis 2002;8:422), testicular endothelium, white blood cells (Blood 1994;83:2451)

Positive staining (disease): AML-M6 (Mod Path 2000;13:407), drug-resistant epileptic human brain (BMC Med 2004 Oct 9;2:37); see also malignancies above under “MDR1 expression is poor prognostic factor”

Micro images: normal - duodenum (fig C/D); heart (NF=nonfailing/normal heart); lung #1 (fig 1A); #2 (fig D/E); nasal mucosa (fig 1C); retinal pigment epithelium

carcinoma - bladder; breast #1; #2 (fig 1-7); #3 (fig D); #4-pre- (fig C) and post-chemotherapy (fig D); #5 (fig 2); gallbladder (fig 2); hepatocellular carcinoma #1; #2 (globular intracytoplasmic staining); #3 (fig 1A); lung (fig 3); pituitary adenoma (fig 2); renal cell; retinoblastoma #1; #2 (cytoplasmic staining); immunofluorescence

References: OMIM 171050, Oncogene 2003;22:7468, Wikipedia

CD244

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Also called Natural Killer cell receptor 2B4

Regulates NK and T cell function in multiple ways (J Immunol 2005;175:2045)

Coexpression of 2B4 and CD160 defines a CD8+ T lymphocyte subpopulation with high cytolytic effector activity (Eur J Immunol 2006;36:2359)

Binds to CD48 (J Immunol 2006;176:4646), and CD244-CD48 interactions prevent NK cells from killing each other (Blood 2007;110:2020)

Functional changes are associated with X linked lymphoproliferative disease (J Exp Med 2000;192:337, J Immunol 2000;165:2932)

Diagrams: NK cell receptors

Uses: no significant clinical use by pathologists

Positive staining (normal): NK cells, CD8+ T cells, monocytes and basophils (Eur J Immunol 1999;29:1676), eosinophils (J Immunol 2005;174:110), spleen (Tissue Antigens 1999;54:27)

References: OMIM 605554

CD245

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Also called p220/240

Very little information is available for CD245 directly; appears to be identical to NPAT (nuclear protein, ataxia-telangiectasia locus)

NPAT links S phase cyclin E/Cdk2 kinase activity to replication-dependent histone gene transcription (Biochemistry 2006;45:15915, Mol Cell Biol 2005;25:6140)

Diagrams: G1-S transition

Uses: no significant clinical use by pathologists

Positive staining (normal): T cells (some), other white blood cells with varying intensity (Washington State Univ)

CD246

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Also called ALK or ALK-1

Anaplastic lymphoma kinase gene at 2p23

Is NOT the same as Ki-1/CD30, as indicated by some references

Membrane spanning tyrosine kinase receptor; ligand is growth factor pleiotrophin

Normally expressed in developing nervous system and weakly in adult nervous system

In anaplastic large cell lymphoma, is usually fused with NPM (nucleophosmin) gene via t(2;5)(p23;q35), but also variants (Genes Chromosomes Cancer 2002;34:354)

ALK negative cases of primary anaplastic large cell lymphoma are associated with trisomy 2 (Mod Path 2005;18:235), consensus criteria for diagnosis are lacking (AJCP 2007;127:707)

ALK mutation causes hereditary hemorrhagic telangiectasia type 2 (J Dent Res 2006;85:705)

Prognostic significance: ALK+ tumors have favorable prognostic significance in anaplastic large cell lymphomas [ALCL] (Blood 1999;93:3913), including primary CNS ALCL (AJSP 2003;27:487) and inflammatory myofibroblastic tumors (AJSP 2007;31:509)

Interpretation: usually cytoplasmic and nuclear staining

Uses: prognostic value in anaplastic large cell lymphoma and inflammatory myofibroblastic tumor (see above), differentiate inflammatory myofibroblastic tumor (ALK+) from ALK negative spindled neoplasms in soft tissue (AJSP 2001;25:1364) and bladder (Mod Path 2007;20:592)

Positive staining (normal): embryonic neurons of CNS/PNS; weakly positive in adult brain

Positive staining (tumors): T/null cell anaplastic lymphomas (most), inflammatory myofibroblastic tumor (AJSP 2001;25:1364, AJSP 2001;25:761); diffuse large B cell lymphoma (rarely, Mod Path 2007;20:310); low level expression in some rhabdomyosarcomas, lipogenic tumors, Ewing’s/PNET, MFH, leiomyosarcoma and other soft tissue tumors (Hum Path 2004;35:711)

Negative staining: fibromatosis, GIST, nodular fasciitis, normal lymphoid tissue

Micro images: alveolar rhabdomyosarcoma (dot-like cytoplasmic staining-fig B); anaplastic lymphoma #1; #2 (fig C); anaplastic lymphoma-various images #1; #2; #3 (quality control); diffuse large B cell lymphoma (fig B); inflammatory myofibroblastic tumor #1 of bladder (fig d); #2 of abdomen (fig 2A); #3 of larynx (fig 2c); #4-site unspecified (fig B); #5-site unspecified (fig A); neuroblastoma (weak)

References: OMIM 105590

CD247

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Also called T cell receptor zeta chain

Forms T cell-CD3 receptor complex with TCR alpha/beta and gamma/delta heterodimers and CD3-gamma, delta and epsilon (Proc Natl Acad Sci USA 1988;85:9709)

Couples antigen recognition to several intracellular signal transduction pathways; low expression causes impaired immune response

Low expression in tumor infiltrating T cells in various disorders - cancer of kidney (Cancer Invest 2004;22:871) and stomach (Cancer 2002;94:1437), Hodgkin’s lymphoma (Blood 1996;88:236); also active tuberculosis (J Infect Dis 2006;194:1385), systemic lupus erythematosus (J Immunol 2002;169:6048, Adv Med Sci 2006;51:181), normal pregnancy but not preeclampsia (Am J Obstet Gynecol 2003;189:843)

Defects cause primary T-cell immunodeficiency (OMIM 610163)

Diagrams: TCR complex; T cell activation

Uses: no significant clinical use by pathologists

Positive staining (normal): T cells

Micro images: gastric carcinoma intratumoral lymphocytes compared to CD3 epsilon (fig A): #1-normal expression (fig B); #2-reduced expression (fig B)

References: OMIM 186780

CD248

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Also called endosialin, tumor endothelial marker 1 (TEM1)

Cell surface glycoprotein associated with tumors - traditionally thought present in vascular endothelial cells (Proc Natl Acad Sci USA 1992;89:10832, J Biol Chem 2001;276:7408), but may actually be marker of stromal fibroblasts (FEBS Lett 2005;579:2569)

Not present (or weak) in non-tumor associated endothelium

Uses: no significant clinical use by pathologists

Positive staining (normal): endometrium; embryos (Cancer Res 2001;61:6649), fibroblasts and pericytes during lymphoid tissue development (FEBS Lett 2007;581:3550); RNA at low/moderate levels in many organs

Positive staining (disease): MFH and other sarcomas, some capillaries and fibroblasts in carcinomas; endothelium of high grade brain tumors (J Neuropathol Exp Neurol 2004;63:1274); RNA at low/moderate levels in carcinomas (Cancer Immun 2005 Aug 3;5:10)

Micro images: normal tissue; normal colon and colorectal carcinoma (see TEM1); various tumors #1 (scroll down for color images); #2; #3

References: OMIM 606064

CD249

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Also called ENPEP, glutamyl aminopeptidase, differentiation antigen gp160, aminopeptidase A

Regulates blood pressure via renin-angiotensin system (J Biol Chem 2006;281:23503)

Uses: no significant clinical use by pathologists

Positive staining (normal): kidney; also brain, heart, liver, lung, placenta, skeletal muscle, pancreas (Genomics 1993;17:657)

Positive staining (disease): cervical neoplasia (Lab Invest 2004;84:639), renal cell carcinoma-some (Proc Natl Acad Sci USA 1993;90:7069)

Micro images: cervical HSIL and squamous cell carcinoma

References: OMIM 138297

CD273

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Programmed cell death ligand 2; also called B7DC

Involved in the costimulatory signal, essential for T lymphocyte proliferation and interferon gamma production

Found in the plasma membrane

CD274

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Programmed cell death ligand 1; also called B7-H1

Involved in the costimulatory signal, essential for T lymphocyte proliferation and production of interferon gamma and IL10

Found in the plasma membrane and intracellular membrane

CD278

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Also called ICOS

Enhances basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, upregulation of molecules that mediate cell-cell interaction and effective help for antibody secretion by B-cells. Essential both for efficient interaction between T and B-cells and for normal antibody responses to T-cell dependent antigens. Plays a critical role in CD40-mediated class switching of immunoglobin isotypes

A type I membrane protein

Defects cause ICOS deficiency (MIM:607594), a form of common variable immunodeficiency characterized by recurrent bacterial infections of the respiratory and digestive tracts, but without splenomegaly, autoimmune disease, sarcoid-like granulomas, overt T cell immunodeficiency

Present in: activated T cells, tonsillar T cells, fetal and newborn thymic medulla

References: Swiss-Prot entry

CD281   TLR1_HUMAN   Q15399  601194  TLR1             Toll-like receptor 1 (Toll/interleukin-1 receptor-like) (TIL)

CD282   TLR2_HUMAN   O60603  603028  TLR2; TIL4       Toll-like receptor 2 (Toll/interleukin-1 receptor-like protein 4)

CD283   TLR3_HUMAN   O15455  603029  TLR3             Toll-like receptor 3

CD284   TLR4_HUMAN   O00206  603030  TLR4             Toll-like receptor 4

CD289   TLR9_HUMAN   Q9NR96  605474  TLR9             Toll-like receptor 9

End of CD markers CD100 to CD400 Chapter

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CD1 to CD49

CD50 to CD99

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