GLUTATHIONE-S-TRANSFERASE-PI EXPRESSION AND GLUTATHIONE CONCENTRATIONIN OVARIAN-CARCINOMA BEFORE AND AFTER CHEMOTHERAPY

BACKGROUND. To clarify the role of glutathione (GSH) in the chemothera py resistance of ovarian carcinoma, the authors examined the expressio n of glutathione S-transferase-pi (GST-pi) and the concentration of gl utathione in tumors before and after chemotherapy in the same patients . METHODS, The cohort for this study comprised 20 patients with ovaria n carcinoma who had residual disease after primary surgery. These pati ents received two to three courses of postoperative chemotherapy, then underwent surgery for a second time. Chemotherapy consisted of 50 mg/ m(2) cisplatin, 40 mg/m(2) doxorubicin, and 400 mg/m(2) cyclophosphami de. The expression of GST-pi in tumors was determined by immunohistoch emical staining and Western blot analysis. GSH concentration was measu red by an enzymatic assay. RESULTS, Of the 20 patients, 10 responded t o chemotherapy and 10 did not. Immunohistochemical staining for GST-pi was positive in 3 tumors among the 10 responders and in 7 tumors amon g the 10 nonresponders, but Western blot analysis detected GST-pi expr ession in all tumors. Among the responders, GST-pi after chemotherapy increased in one patient, was unchanged in two patients, and decreased in seven patients. Among nonresponders, GST-pi increased in six patie nts, was unchanged in one patient, and decreased in three patients. Th e ratio of GST-pi density in tumors after chemotherapy to GST-pi densi ty before chemotherapy was significantly higher in nonresponders than in responders (2.0 +/- 1.1 vs. 0.6 +/- 0.4). The concentration of GSH in tumors was widely distributed, but it was found that the ratio of G SH concentration in each tumor after chemotherapy to GSH concentration before chemotherapy was significantly higher for nonresponders than f or responders (3.0 +/- 1.3 vs. 0.6 +/- 0.3). CONCLUSIONS, Increased le vels of GST-pi expression after chemotherapy are linked to drug resist ance in patients with ovarian carcinoma. (C) 1997 American Cancer Soci ety.