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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

Departments of Gynecological Oncology [H. J. G. A., A. G. J. v. d. Z.], Medical Oncology [E. G. E. d. V., P. H. B. W.], and Pathology [A. J. H. S.], University Hospital Groningen, 9700 GB Groningen, the Netherlands; Department of Gynecology, Gynecologic Oncology, and Breast Cancer Unit [D. K., M. M., F. G., S. D.] and Department of Pathology [R. A.], S’Anna Hospital, University of Turin, Italy 10126; Department of Pathology, Free University Hospital Amsterdam, 1081 HV Amsterdam, the Netherlands [R. J. S., G. L. S.]; and Department of Molecular Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands [M. K.]

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 resistance-associated proteins P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), canalicular multispecific organic anion transporter (c-MOAT/MRP2), and lung resistance protein (LRP) in ovarian carcinoma. Expression of P-gp, MRP1, MRP2, and LRP was determined by immunohistochemistry of frozen tissue sections of 115 ovarian carcinoma patients and related to clinicopathological factors, response to chemotherapy, and progression-free survival. P-gp expression was observed in 20 of 115 (17%), MRP1 in 51 (44%), MRP2 in 19 (16%), and LRP in 85 (74%) tumors. Expression of MRP1 was related to MRP2 (P < 0.0001) and P-gp (P < 0.001) expression, whereas LRP expression 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-line chemotherapy in 59 evaluable patients nor to progression-free survival in all patients. On multivariate analysis, only stage and residual tumor were independent prognostic factors for survival. In conclusion, in ovarian carcinoma, MRP1 expression is associated with MRP2 and P-gp expression, whereas LRP expression is associated with favorable clinicopathological characteristics. Assessment of P-gp, MRP1, MRP2, or LRP does not allow prediction of response to chemotherapy or survival in ovarian carcinoma.

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