Immunohistochemical expression of topoisomerase II alpha (Topo II alpha) and multidrug resistance-associated protein (MRP), plus chemosensitivity testing, as chemotherapeutic indices of ovarian and endometrial carcinomas

Objective. The purpose of this study was to investigate the chemosensitive and chemoresistant indices of gynecologic malignancies. Methods: We studied the expression of topoisomerase II alpha (Topo II alpha) and multidrug res istance-associated protein (MRP), and then correlated them with the in vitr o chemosensitivities of gynecologic tumor cells using immunohistochemistry and a tetrazolium dye (MTT) assay. Results: In the 19 ovarian carcinomas ex amined, the mean Topo II a index (%) and the tumor cell growth inhibition r ate (I.R.: %) for doxorubicin and etoposide in the clear cell adenocarcinom as [15.8, 21.4, 32.3] were all lower than in the endometrioid [33.9; p < 0. 001, 58.3, 61.9; p < 0.05, respectively] and serous adenocarcinomas [43.6; p < 0.001, 75.0, 79.8, p < 0.01, respectively]. Comparing these markers wit h the clinical response to chemotherapy, the overall predictive accuracy of the Topo II alpha index and the MTT assay was 87.5% (14/16) and 81.3% (13/ 16), respectively. In the 24 endometrial carcinomas examined, the mean Topo II alpha index and the LR for doxorubicin and etoposide in the G1 carcinom as [22.2, 26.8, 21.5] were significantly lower than in the G2/G3 carcinomas [38.4, 54.0, p < 0.001, 40.5; p < 0.05]. Furthermore, strong MRP expressio n (greater than or equal to 50%) was detected in 13 (93%) of the 14 G1 carc inomas, but in only 4 (44%) of the 9 G2/G3 carcinomas (p < 0.05). Conclusio ns: The Topo II alpha index and the results of in vitro chemosensitivity te sting may be of assistance in selecting the appropriate chemotherapeutic dr ugs against gynecologic malignancies based on their histological type and d ifferentiation, along with MRP expression.