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Glutathione concentration may be a useful predictor of response to second‐line chemotherapy in patients with ovarian cancer
Author(s) -
Kigawa Junzo,
Minagawa Yukihisa,
Kanamori Yasunobu,
Itamochi Hiroaki,
Cheng Xiusi,
Okada Makoto,
Oishi Tetsuro,
Terakawa Naoki
Publication year - 1998
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(19980215)82:4<697::aid-cncr12>3.0.co;2-t
Subject(s) - glutathione , etoposide , cisplatin , chemotherapy , ovarian cancer , medicine , western blot , immunohistochemistry , cancer , oncology , blot , glutathione s transferase , gastroenterology , pathology , endocrinology , biology , enzyme , biochemistry , gene
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. Cancer 1998;82:697‐702. © 1998 American Cancer Society.