CD Markers - CD100 to CD400 - Printer Friendly Version

(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

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)

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)

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)

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)

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

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

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)

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

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

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