Expression of multidrug resistance markers ABCB1 (MDR-1/P-gp) and ABCC1 (MRP-1) in renal cell carcinoma

Abstract

Background: Renal cell carcinoma patients respond poorly to conventional chemotherapy, this unresponsiveness may be attributable to multidrug resistance (MDR). The mechanisms of MDR in renal cancer are not fully understood and the specific contribution of ABC transporter proteins which have been implicated in the chemoresistance of various cancers has not been fully defined in this disease.

Methods: In this retrospective study the expression of two of these transporter efflux pumps, namely MDR-1 P-gp (ABCB1) and MRP-1 (ABCC1) were studied by immunohistochemistry in archival material from 95 renal cell carcinoma patients.

Results: In the first study investigating MDR-1 P-gp and MRP-1 protein expression patterns in renal cell carcinoma patients, high levels of expression of both efflux pumps are observed with 100% of tumours studied showing MDR-1 P-gp and MRP-1 positivity.

Conclusion: Although these findings do not prove a causal role, the high frequency of tumours expressing these efflux pumps suggests that they may be important contributors to the chemoresistance of this tumour type.

Figure 1

Immunohistochemical analysis of MDR-1 P-gp and MRP-1 protein expression in RCC. (A) RCC tumour showing positive MDR-1 P-gp staining with strong MDR-1 positivity observed, score (4+3) (scale bar = 100 μm) and (B) MDR-1 P-gp positive RCC with moderate positivity observed, score (2+2) (scale bar = 100 μm) (C) MRP-1 positive tumour showing intense MRP-1 positive staining, score (4+3) (scale bar = 100 μm) and (D) MRP-1 positive RCC with moderate positivity observed, score (2+2) (scale bar = 100 μm). (Original magnifications of all photomicrographs ×40).