Glutathione concentration may be a useful predictor of response to second-line chemotherapy in patients with ovarian cancer

Abstract

BACKGROUND. No useful predictor of resistance or sensitivity to second- line chemotherapy is known for ovarian cancer. The objective of this prospective study was to determine the utility of tumor glutathione S- transferase-π (GST-π) expression or glutathione (GSH) concentration in predicting ovarian cancer patients' responses to second-line chemotherapy. METHODS. Tumor samples were obtained from 26 patients with relapsed epithelial ovarian cancer 3-4 weeks before the initiation of second-line chemotherapy with etoposide (daily on Days 1-5) and cisplatin (on Day 5). The expression of GST-π in tumor samples was determined by immunohistochemical staining and Western blot analysis. GSH concentration was measured by an enzymatic assay. RESULTS. The response rate was 38.4%. The estimated 3-year survival rate for the responders (66.7%) significantly exceeded that for the nonresponders (9.1%). Expression of GST-π by immunohistochemical staining was more frequently observed in nonresponders (2 of 10 responders vs. 11 of 16 nonresponders). Western blot analysis detected GST-π in all cases. There was no significant difference in the relative density values of the GST-π Western blot analysis between the two groups. The mean value of GSH concentration in nonresponders was significantly higher than in responders (18.4 ± 9.7 vs. 7.5 ± 8.2 μg/mg protein). GSH concentration was below the cutoff point (10.3 μg/mg protein) in all responders except one. CONCLUSIONS. Second-line chemotherapy consisting of etoposide and cisplatin is effective in the treatment of relapsed epithelial ovarian cancer. In addition, tumor concentration of GSH may be a useful predictor of the response to this therapy.