THE RELATIONSHIP BETWEEN TUMOR GLUTATHIONE CONCENTRATION, GLUTATHIONE-S-TRANSFERASE ISOENZYME EXPRESSION AND RESPONSE TO SINGLE-AGENT CARBOPLATIN IN EPITHELIAL OVARIAN-CANCER PATIENTS

There is evidence to suggest that glutathione (GSH) and glutathione-S- transferases (GST) are important factors in determining sensitivity to cytotoxic drugs in vitro and in preclinical in vivo model systems. To define the relationship between tumour GSH concentration, GST isoenzy me expression and response to carboplatin in epithelial ovarian cancer (EOC), tumour samples from 39 patients with assessable disease after primary surgery were analysed for GSH content and GST expression. Resp onse was assessed after completing six courses of single agent carbopl atin therapy. GSH was measured by high performance liquid chromatograp hy (HPLC) in fresh tumour samples taken at primary laparotomy. GST iso enzyme expression was assessed by immunohistochemistry of fixed tumour material using antibodies specific for pi, alpha and mu classes. CST isoenzyme expression was defined as positive if the staining intensity was strong and more than 10% of tumour cells were involved. The mean GSH concentrations were: 8351+/-4496, 7211+/-5026, 6559+/-4573 and 375 8+/-1885 (nmol g(-1) tissue dry weight mean+/-s.d.) for tumours from p atients who subsequently achieved a complete response (CR, n=18), part ial response (PR, n=10) or who had static disease (SD, n=7) or progres sive disease (PD, n=4) respectively. There was no relationship between GSH concentration and response (ANOVA, P=0.32). There were also no re lationship between GST isoenzyme expression and response (P Fisher's e xact test 0.51-0.55 and chi-squared test 0.98-0.99). In conclusion, th ere was no association between the concentration of GSH or expression of GST isoenzymes and response to single agent carboplatin in primary previously untreated EOC.