Drug resistance-associated markers P-glycoprotein, multidrug resistance-associated protein 1, multidrug resistance-associated protein 2, and lung resistance protein as prognostic factors in ovarian carcinoma

Intrinsic and/or acquired resistance to chemotherapy is the major obstacle to overcome in the treatment of patients with ovarian carcinoma. The aim of the present study was to investigate the prognostic value of drug resistan ce-associated proteins P-glycoprotein (P-gp), multidrug resistance-associat ed protein 1 (MRP1), canalicular multispecific organic anion transporter (c -MOAT/MRP2), and lung resistance protein (LRP) in ovarian carcinoma. Expres sion of P-gp, MRP1, MRP2, and LRP was determined by immunohistochemistry of frozen tissue sections of 115 ovarian carcinoma patients and related to cl inicopathological factors, response to chemotherapy, and progression-free s urvival. P-gp expression was observed in 20 of 115 (17%), MRP1 in 51 (34%), MRP2 in 19 (16%), and LRP in 85 (74%) tumors. Expression of MRP1 was relat ed to MRP2 (P < 0.0001) and P-gp (P < 0.001) expression, whereas LRP expres sion was more frequently observed in patients with early stage (P < 0.01), lower grade (P < 0.05), and smaller residual tumor (P < 0.05). Early stage (P < 0.001), smaller residual tumor (P < 0.001), and lower differentiation grade (P < 0.05) were related to longer (progression-free) survival. P-gp, MRP1, MRP2, and LRP expression were neither related to response to first-li ne chemotherapy In 59 evaluable patients nor to progression-free survival i n all patients. On multivariate analysis, only stage and residual tumor wer e independent prognostic factors for survival. In conclusion, in ovarian ca rcinoma, MRP1 expression is associated with MRP2 and P-gp expression, where as LRP expression is associated with favorable clinicopathological characte ristics. Assessment of P-gp, MRP1, MRP2, or LRP does not allow prediction o f response to chemotherapy or survival in ovarian carcinoma.