Role of metallothionein in cisplatin sensitivity of germ‐cell tumours

Cisplatin (CDDP) is an extremely active drug in the treatment of germ‐cell tumours. Earlier, we found an unexpected inverse correlation between the total amount of sulfhydryl groups and CDDP sensitivity in a panel of 3 human germ‐cell‐tumour and 3 colon‐carcinoma cell lines. Major components of the sulfhydryl groups are glutathione and metallothionein (MT). We further investigated a possible role of MT in the CDDP sensitivity of germ‐cell tumours. MT levels and functionality of the germ‐cell‐tumour and colon‐carcinoma cell lines were found to be inversely correlated with CDDP sensitivity. No difference in sub‐cellular localization of MT could be observed among the types of cell lines. In agreement with the in vitro data, immunohistochemical detection of MT was high in 11/14 primary human germ‐cell tumours and low in 7/7 human colon carcinomas. MT‐protein expression in primary germ‐cell tumours did not discriminate between responding and non‐responding patients. As compared with the primary tumours, MT‐protein expression decreased in 5/7 post‐chemotherapy residual vital tumours or remained undetectable (2/7). MT‐protein expression in the germ‐cell tumours was not related to total p53‐protein expression. In summary, over‐expression of MT was found in germ‐cell tumours, both in cell lines and in human tumours. Although MT‐protein over‐expression seems to be associated with the CDDP sensitivity of germ‐cell tumours, MT‐protein expression in primary germ‐cell tumours did not differ between responding and non‐responding patients and therefore cannot be used to predict response to chemotherapy. Int. J. Cancer 85:777–781, 2000. © 2000 Wiley‐Liss, Inc.