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

Evgeny Yakirevich1, Edmond Sabo, Inna Naroditsky

  • 1Department of Pathology, Carmel Medical Center and Rappaport Faculty of Medicine, Technion University, Haifa, Israel. eyakirevich@lifespan.org

Gynecologic Oncology
|October 4, 2005
PubMed
Abstract

Insights

Multidrug resistance (MDR) in ovarian cancer is linked to drug transporter proteins. P-glycoprotein (P-gp) expression is a significant predictor of poor survival and chemotherapy resistance in ovarian serous carcinoma patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Multidrug resistance (MDR) hinders effective chemotherapy for ovarian carcinoma.
  • MDR is often associated with the overexpression of drug transporters like P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), and lung resistance protein (LRP).

Purpose of the Study:

  • To assess the prevalence and prognostic value of MDR-related proteins (P-gp, MRP1, LRP) in ovarian serous carcinomas.
  • To correlate the expression of these proteins with apoptosis-related markers (p53, bcl-2, bax).

Main Methods:

  • Immunohistochemical analysis of 60 ovarian serous carcinoma tissues.
  • Quantification of P-gp, MRP1, LRP, p53, bcl-2, and bax protein expression levels.
  • Statistical analysis including univariate and multivariate survival analyses.

Main Results:

  • High expression rates were observed for MRP1 (65%), p53 (75%), LRP (45%), bax (50%), and bcl-2 (41.7%).
  • P-gp expression showed a significant inverse correlation with patient survival (P=0.015) and was higher in chemotherapy-unresponsive tumors (P=0.009).
  • Multivariate analysis identified FIGO stage and P-gp expression as independent negative predictors of survival.

Conclusions:

  • P-glycoprotein (P-gp) expression is a potential independent prognostic factor for survival in ovarian serous carcinoma.
  • P-gp immunostaining can help differentiate between chemoresponsive and chemoresistant patient groups.

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