Stains & CD markers
MDR / CD243
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: CD243
MDR / CD243
Author: Nat Pernick, M.D.
Last author update: 1 April 2010
Last staff update: 5 September 2023
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: CD243
Table of Contents
Definition / general | Terminology | Pathophysiology | Clinical features | Uses by pathologists | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Additional referencesCite this page: Hamilton K, Pernick N. MDR / CD243. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainsMDR.html. Accessed November 27th, 2024.
Definition / general
- "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
- P glycoprotein is product of MDR1 gene
- Also called MDR1 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 / CerbB2 (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 JSB1 appears to have similar behavior as C494, as it cross reacts with pyruvate carboxlyase (J Histochem Cytochem 1995;43:1187)
Pathophysiology
- 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 features
- Specific polymorphism associations: ulcerative colitis (Hum Mol Genet 2006;15:797), Parkinson disease reduced risk (Arch Neurol 2005;62:460)
- Response to chemotherapy in small cell lung cancer (Jpn J Clin Oncol 2006;36:137)
Uses by pathologists
- 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 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 tumor staining of endothelial cells (Am J Clin Pathol 2002;117:484)
Microscopic (histologic) images
Images hosted on other servers:
Normal tissue:
Lung, fig 1A
Retinal pigment epithelium
Carcinoma:
Bladder
Breast
Hepatocellular carcinoma, globular intracytoplasmic stain
Renal cell carcinoma
Retinoblastoma, figs 1, 2
Immunofluorescence
Positive staining - normal
- 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 staining - disease
- May cross react with HER2/CerbB2
- AMLM6 (Mod Pathol 2000;13:407)
Additional references
