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

Anticancer Res. 2007 May-Jun;27(3B):1449-52.

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.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma / drug therapy*
  • DNA / analysis
  • DNA / metabolism
  • DNA Methylation / drug effects*
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Humans
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • MutL Protein Homolog 1
  • Nuclear Proteins / genetics*
  • Ovarian Neoplasms / drug therapy*
  • Platinum Compounds / therapeutic use*
  • Promoter Regions, Genetic
  • Sequence Analysis, DNA

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • MLH1 protein, human
  • Nuclear Proteins
  • Platinum Compounds
  • DNA
  • MutL Protein Homolog 1