Metallothionein expression in epithelial ovarian cancer: effect of chemotherapy and prognostic significance

Background and purpose: Regimens containing platinum drugs continue to be a mongst the most effective therapies for ovarian cancer. However, despite hi gh initial response rates most patients relapse and die of their disease. E levation of metallothionein has been implicated as a mechanism by which tum our cells become resistant to platinum anticancer drugs, although most of t hese studies have been carried out in vitro. This study was carried out to determine whether metallothionein expression was associated with response o r survival in patients with epithelial ovarian cancer. Methods: Metallothio nein was determined by radioimmune assay using frozen ovarian tumour tissue taken either before or following cytotoxic chemotherapy. Results: An incre ase in expression of metallothionein was seen in tumour tissue from patient s who had undergone cytotoxic chemotherapy, although this did not attain si gnificance. However, a preliminary study using biopsy material from the sam e patient, taken both before and after chemotherapy, showed a statistically significant increase in metallothionein. An analysis of these data showed that the level of metallothionein expression was not associated with surviv al or response. Conclusion: These data do not support the hypothesis that m etallothionein expression is a determinant of response in ovarian cancer. T here is some preliminary evidence from the study of paired samples which in dicates that cytotoxic chemotherapy may increase metallothionein expression . An increase in metallothionein was also seen in the study using unmatched biopsies although this did not attain statistical significance, due in par t to the large inter-patient variability in expression of this protein.