Correlation of c-erb B-2 and topoisomerase II alpha mRNA expression in ovarian cancer

Amplification and overexpression of the oncogene c-erbB-2 (HER-2/neu) has b een shown to be associated with poor prognosis in ovarian and breast cancer . In the present study we examined the role of c-erbB-2 for chemoresistance in ovarian cancer. As expected overexpression of c-erbB-2 mRNA in tumor ti ssue was associated with shorter survival of patients with primary ovarian cancer (p=0.0001; n=77). Interestingly, application of a standard chemother apy improved survival of patients with relatively low c-erbB-2 expression ( p=0.013), but not of patients that overexpressed c-erbB-2 (p=0.359). In add ition, expression of c-erbB-2 mRNA correlated with topoisomerase II alpha m RNA (p=0.009), but not with topoisomerase II beta (p=0.221). To examine the hypothesis that coamplified and/or coregulated topoisomerase II alpha cont ributes to resistance of c-erbB-2 overexpressing carcinomas, we tested chem osensitivity of primary cells from an ovarian carcinoma that overexpressed both, c-erbB-2 and topoisomerase II alpha. Combination of carboplatin with non-toxic concentrations of the topoisomerase II-inhibitors etoposide or no vobiocin enhanced toxicity of carboplatin. In contrast the influence of the tyrosine kinase inhibitor emodin was less than additive. The data suggest that topoisomerase II alpha that correlates with c-erbB-2 expression, contr ibutes to resistance of a subgroup of c-erbB-2 overexpressing carcinomas.