Immunohistochemical expression of topoisomerase IIalpha (Topo IIalpha) 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 a(Topo II a) and multidrug resistance-associated protein (MRP), and then correlated them with the in vitro chemosensitivities of gynecologic tumor cells using immunohistochemistry and a tetrazolium dye (MTT) assay. Results: In the 19 ovarian carcinomas examined, the mean Topo II a index (%) and the tumor cell growth inhibition rate (I.R.: %) for doxorubicin and etoposide in the clear cell adenocarcinomas [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 with the clinical response to chemotherapy, the overall predictive accuracy of the Topo II a 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 a index and the I.R for doxorubicin and etoposide in the G1 carcinomas [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 expression (≥50%) was detected in 13 (93%) of the 14 G1 carcinomas, but in only 4 (44%) of the 9 G2/G3 carcinomas (p<0.05). Conclusions: The Topo II a index and the results of in vitro chemosensitivity testing may be of assistance in selecting the appropriate chemotherapeutic drugs against gynecologic malignancies based on their histological type and differentiation, along with MRP expression.