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.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Watanabe Y,Ueda H,Etoh T,Koike E,Fujinami N,Mitsuhashi A,Hoshiai H

subject

Has Abstract

pub_date

2007-05-01 00:00:00

pages

1449-52

issue

3B

eissn

0250-7005

issn

1791-7530

journal_volume

27

pub_type

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