EXPRESSION OF GAMMA-GLUTAMYL-TRANSPEPTIDASE IN STAGE-III AND STAGE-IVOVARIAN SURFACE EPITHELIAL CARCINOMAS DOES NOT ALTER RESPONSE TO PRIMARY CISPLATIN-BASED CHEMOTHERAPY

OBJECTIVE: gamma-Glutamyl transpeptidase activity has been shown to be essential for the nephrotoxicity of cisplatin. The purpose of this st udy was to determine whether expression of gamma-glutamyl transpeptida se in ovarian carcinomas is necessary for the antitumor effect of cisp latin. STUDY DESIGN: Tumor tissue from 18 patients with stage III or I V ovarian serous, papillary carcinoma or poorly differentiated adenoca rcinoma was analyzed for expression of gamma-glutamyl transpeptidase b y histochemical or immunohistochemical staining. Response to cisplatin -based combination chemotherapy was evaluated on the basis of clinical response, progression-free interval, and survival. RESULTS: gamma-Glu tamyl transpeptidase expression in the tumors ranged from 0% to 100% o f the tumor cells gamma-glutamyl transpeptidase positive. Patient surv ival ranged from 15 months to 9 years. Twelve of the 18 patients had a complete response to the initial course of cisplatin-based combinatio n chemotherapy. There was no statistically significant correlation bet ween either response or time to relapse and gamma-glutamyl transpeptid ase expression. However, there was a correlation between high levels o f gamma-glutamyl transpeptidase in the tumor and acute ototoxicity in patients treated with cisplatin. Expression of high levels of gamma-gl utamyl transpeptidase in the tumor was also found to be associated wit h shorter patient survival, suggesting that gamma-glutamyl transpeptid ase might have a role in resistance to drugs used in second- and third -line therapy. CONCLUSIONS: Expression of gamma-glutamyl transpeptidas e in ovarian serous papillary or poorly differentiated adenocarcinomas is not necessary for the antitumor activity of cisplatin. A correlati on was found between high levels of gamma-glutamyl transpeptidase in t he tumor and both increased ototoxicity from cisplatin and decreased p atient survival. These data suggest that administering an inhibitor of gamma-glutamyl transpeptidase activity to block the nephrotoxicity of cisplatin would not interfere with its therapeutic effect.