Expression of MDR1 P-glycoprotein and MRP-1 proteins in melanoma

AACR Centennial Conference: Translational Cancer Medicine-- July 20-23, 2008; Monterey, CA B5 Background: Multiple drug resistance (MDR) is a phenomenon whereby cancer cells are resistant to a broad range of structurally and mechanistically unrelated drugs; either inherently or acquired, following exposure to chemotherapy (CRx) drug(s). ATP-dependent membrane-bound drug efflux pumps (EP), including MDR1 P-glycoprotein (MDR1 P-gp) and MRP-1, may be mediators of clinically relevant MDR. Here we studied the prevalence of MDR1 P-gp and MRP-1 in melanomas which are highly CRx-resistant. Methods: In this retrospective study we analysed the expression of MDR1 P-gp and MRP-1 protein in 191 melanoma specimens by immunohistochemistry (IHC). Anti-MDR1 P-gp monoclonal antibody, 6/1C, and anti-MRP-1 monoclonal antibody, P2A8(6), generated in our laboratory, were used for this analysis. IHC staining was evaluated semi-quantitatively by two independent observers. Results: EP expression is common in melanoma. 96.3% (184/191) of cases were positive for MRP-1, 82.7% (158/191) expressed MDR1 P-gp, with approx. 79.5% expressing both MRP-1 and MDR1 P-gp. Only 1/191 specimens analysed expressed neither of these EP. Conclusions: Expression of one or both EP is common in melanoma. These observations do not prove causality, but they are consistent with the hypothesis that EP might be, at least partly, responsible for MDR in this form of cancer.