Multidrug resistance-related phenotype and apoptosis-related protein expression in ovarian serous carcinomas

Abstract: Objective. : Multidrug resistance (MDR) to chemotherapy is a major obstacle in attempts to improve the clinical outcome of ovarian carcinoma patients. The MDR-related phenotype is associated with over-expression of certain drug transporters, such as P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and lung resistance protein (LRP). The aim of this study was to evaluate the extent and prognostic significance of MDR-related protein expression in ovarian serous carcinomas. In addition, we correlated expression of these proteins with the apoptosis-related proteins p53, bcl-2, and bax. Methods. : Consecutive sections from 60 cases of ovarian serous carcinoma were assessed immunohistochemically for expression of P-gp, MRP1, LRP, p53, bcl-2, and bax. The level of protein expression was scored based on staining intensity and extent. Results. : Strong P-gp expression was observed in 12 (20%), MRP1 in 39 (65%), LRP in 27 (45%), p53 in 45 (75%), bcl-2 in 25 (41.7%), and bax in 30 (50%) of the 60 tumors. MRP1 expression was associated with both p53 and bcl-2 expressions (P = 0.01 and P = 0.03, respectively). Univariate analysis of survival revealed a significant inverse correlation between P-gp expression and patient survival (P = 0.015). Moreover, P-gp expression was significantly increased in tumors of patients unresponsive to chemotherapy (P = 0.009). Multivariate analysis revealed that only FIGO stage and P-gp expression were useful negative independent predictors of survival (P = 0.035 and P = 0.045, respectively). Conclusions. : Our pilot study demonstrates that P-gp expression may be a reliable independent prognostic factor of survival in patients with ovarian serous carcinoma. Moreover, P-gp immunostaining may be useful for dividing ovarian carcinoma patients into chemoresponsive and chemoresistant groups. [Copyright &y& Elsevier]