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

Regimens containing platinum drugs continue to be amongst the most effective therapies for ovarian cancer. However, despite high initial response rates most patients relapse and die of their disease. Elevation of metallothionein has been implicated as a mechanism by which tumour cells become resistant to platinum anticancer drugs, although most of these studies have been carried out in vitro. This study was carried out to determine whether metallothionein expression was associated with response or survival in patients with epithelial ovarian cancer. Metallothionein was determined by radioimmune assay using frozen ovarian tumour tissue taken either before or following cytotoxic chemotherapy. An increase in expression of metallothionein was seen in tumour tissue from patients who had undergone cytotoxic chemotherapy, although this did not attain significance. However, a preliminary study using biopsy material from the same 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 survival or response. These data do not support the hypothesis that metallothionein expression is a determinant of response in ovarian cancer. There is some preliminary evidence from the study of paired samples which indicates 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 part to the large inter-patient variability in expression of this protein.