CD Markers - CD243

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CD Markers

CD243

Authors: Kara Hamilton, M.S., Nat Pernick, M.D., PathologyOutlines.com, Inc.

Revised: 21 September 2012, last major update April 2010

Definition

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

● Also mediates the ATP-driven efflux of drugs from multidrug-resistant cancer and HIV-infected cells.

Terminology

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● P glycoprotein is product of MDR1 gene

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

● Antibody C219 binds to both ATP-binding regions of P-glycoprotein and inhibits its ATPase activity and drug binding capacity; widely used as a tumor marker, but cross-reacts with HER2/c-erbB2 (Proc Natl Acad Sci USA 1999;96:13679)

● Antibody C494 detects an internal cellular epitope present only on the Mdr1 isoform of P-glycoprotein with strong plasma membrane staining patterns; it cross reacts with pyruvate carboxylase, an abundant mitochondrial enzyme (weak, homogeneous, cytoplasmic or granular patterns), but unlike C219, it does not cross react with Mdr3.

● Antibody JSB-1 appears to have similar behavior as C494, as it cross reacts with pyruvate carboxlyase (J Histochem Cytochem 1995;43:1187)

Pathophysiology

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● Assumed to function as ATP-dependent drug efflux pump with broad substrate specificity

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

● 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)

● Present in plasma membranes, not mitochondrial membranes (Exp Cell Res 2007;313:3100)

Clinical information

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● 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)

Uses

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● 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 Pathol 1998;29:594)

- nasopharyngeal carcinoma (Hum Pathol 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 sarcoma-all ages (Hum Pathol 2005;36:994) and in children (J Clin Oncol 1990;8:689)

- Wilm’s tumor-staining of endothelial cells (Am J Clin Pathol 2002;117:484)

Positive stains - normal

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● Typically expressed in cells with excretory and secretory functions

● May cross react with myosin

● Also expressed in:

- 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 stains - not malignant

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● drug-resistant epileptic human brain (BMC Med 2004 Oct 9;2:37);

Positive stains - malignancies

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● May cross react with HER2/c-erbB2

● AML-M6 (Mod Pathol 2000;13:407)

● see also malignancies above under “MDR1 expression is poor prognostic factor”

Micro images

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Normal tissues

Duodenum (fig C/D) Lung #1 (fig 1A) #2 (fig D/E)

Retinal pigment epithelium

Carcinoma

Bladder Breast #1 #2 (fig 1-7)

Hepatocellular carcinoma #1; #2 Renal cell

(globular intracytoplasmic staining)

Retinoblastoma #1; #2 Immunofluorescence

(cytoplasmic staining)

Additional references

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

End of CD Markers > CD243

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