ABC transporters in the development of platinum drug resistance in serous ovarian carcinoma

Abstract

Introduction. Serous ovarian carcinoma is a group of extremely aggressive malignant tumors with high mortality rates; today, it remains the most prognostically unfavorable gynecologic cancer in the world. One of the causes is the development of multidrug resistance after administration of various chemotherapy regimens. Therefore, the search for effective markers of resistance to chemotherapy in this disease is promising. The purpose of this study was to analyze expressions of ABC transporters Pgp (ABCB1) and BCRP (ABCG2) in cells of high-grade serous ovarian carcinomas in patients with varying sensitivity to platinum-based polychemotherapy. Materials and methods. Tumor tissues of 100 patients aged 29–79 years with high-grade serous ovarian carcinomas and stages IIIC–IV were studied with immunohistochemical method with rabbit P-glycoprotein 1 (Pgp or MDR1) polyclonal antibodies and by the Reveal Polyvalent HRP-DAB Detection System with mouse monoclonal BCRP antibodies (JF0994 clone). We used the Statistica 13.0 program (StatSoftInc., USA) to analyze the results. We determined the Mann–Whitney U and Pearson’s χ² values, as well as odds ratios with CI. Results. In groups with platinum resistance and platinum sensitivity, there prevailed patients with Pgp+ (98% and 68%) and BCRP+ (90% and 81.4%). Mann–Whitney U-test showed that in cancer cells in platinum-resistant patients, the expression of Pgp and BCRP (70;40–100 and 65;45–90) was 1.8 (p=0.003) and 1.9 times (p=0.013) higher, respectively, than in platinum-sensitive patients (40;4–65 and 35;10–60). Conclusion. The results on the Pgp marker show that it can be used as a predictive factor in high-grade serous ovarian carcinomas. Keywords: serous ovarian carcinoma, multidrug resistance, ABC transporters, Pgp, BCRP