A change in promoter methylation of hMLH1 is a cause of acquired resistance to platinum-based chemotherapy in epithelial ovarian cancer.

Abstract

BACKGROUND: Acquired resistance to platinum-based chemotherapy (Pt-chemo) is a major problem for improving the prognosis for patients with advanced epithelial ovarian cancer (EOC). However, the molecular mechanism of acquired resistance to Pt-chemo is not well understood. MATERIALS AND METHODS: hMLH1 promoter methylation (hMLH1 MET) and hMLH1 protein expression was examined in 36 paired samples of primary and secondary resected tumors by methylation-specific polymerase chain reaction (PCR). RESULTS: No primary tumors exhibited hMLH1 MET, while 56.3% of secondary tumors showed hMLH1 MET. Moreover, no significant correlation was observed between hMLH1 MET and histological subtype, while hMLH1 MET was significantly greater (p < 0.001) in partially responsive secondary tumors compared with no change or progressive disease, and hMLH1 MET also occurred more frequently (p = 0.059) in tumors treated with four or more courses of Pt-chemo. CONCLUSION: A change in hMLH1 MET is a major molecular cause of acquired resistance to Pt-chemo in EOC.