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The relationship between tumour glutathione concentration, glutathione S-transferase isoenzyme expression and response to single agent carboplatin in epithelial ovarian cancer patients

Lookup NU author(s): Dr Andrew Hall, Professor Alan Calvert, Dr James Sunter, Professor Herbie Newell


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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 isoenzyme 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. Response was assessed after completing six courses of single agent carboplatin therapy. GSH was measured by high performance liquid chromatography (HPLC) in fresh tumour samples taken at primary laparotomy, GST isoenzyme expression was assessed by immunohistochemistry of fixed tumour material using antibodies specific for π, α and μ classes. GST 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 3758 ± 1885 (nmol g-1 tissue dry weight mean ± s.d.) for tumours from patients who subsequently achieved a complete response (CR, n = 18), partial response (PR, n = 10) or who had static discase (SD, n = 7) or progressive disease (PD, n = 4) respectively. There was no relationship between GSH concentration and response (ANOVA, P = 0.32). There were also no relationship between GST isoenzyme expression and response (P Fisher's exact rest 0.51-0.55 and chi-squared test 0.98-0.99). In conclusion, there was no association between the concentration of GSH or expression of GST isoenzymes and response to single agent carboplatin in primary previously untreated EOC.

Publication metadata

Author(s): Ghazal-Aswad, S., Hall, A. G., George, M., Sinha, D., Lind, M., Calvert, A. H., Sunter, J. P., Newell, D. R.

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 1996

Volume: 74

Issue: 3

Pages: 468-473

Print publication date: 01/02/1996

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827


PubMed id: 8695367