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


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.


CONCLUSIONS
A change in hMLH1 MET is a major molecular cause of acquired resistance to Pt-chemo in EOC.
Watanabe
Yoh
Y
Department of Obstetrics and Gynecology, Kinki University School of Medicine, Osaka, Japan. watanabe@med.kindai.ac.jp
Ueda
Haruhiko
H
Etoh
Tomomaro
T
Koike
Eiji
E
Fujinami
Nahoko
N
Mitsuhashi
Akiyo
A
Hoshiai
Hiroshi
H
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D004247:DNA / Q000032:analysis / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017671:Platinum Compounds / Q000627:therapeutic use*; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D017671:Platinum Compounds; D004247:DNA; D000070957:MutL Protein Homolog 1