MSH2 promoter hypermethylation in circulating tumor DNA is a valuable predictor of disease-free survival for patients with esophageal squamous cell carcinoma

Eur J Surg Oncol. 2012 Apr;38(4):326-32. doi: 10.1016/j.ejso.2012.01.008. Epub 2012 Jan 23.

Abstract

Background: Tumor-specific alterations of DNA methylation in circulating DNA have been associated with tumor burden and malignant progression. A wealth of information indicating the potential use of DNA methylation in circulating DNA for cancer screening, prognosis and monitoring of the efficacy of anticancer therapies has emerged. In this study, we examined prospectively whether the presence of plasma DNA with tumor characteristics before oesophagectomy is a predictive factor related to disease-free survival (DFS).

Methods: Promoter hypermethylation of MSH2 was analyzed using real-time methylation-specific PCR (real-time MSP) in paired tumor and plasma samples of 209 patients with esophageal squamous cell carcinoma (ESCC).

Results: Aberrant MSH2 methylation was found in 101 of 209 ESCC patients. Of these 101 patients, 77 cases exhibited the same alteration in their plasma DNA. No alterations were found in the plasma DNA of the remaining 108 patients. As a control, we screened for aberrant methylation in the plasma DNA of 60 health individuals. No methylation was found in plasma DNA of these control groups. Follow-up analysis indicated significantly lower DFS for patients with high MSH2 methylation compared to those with MSH2 unmethylation after surgery.

Conclusions: It was suggestted that MSH2 methylation in the plasma would be a good predictor of DFS for these ESCC patients before oesophagectomy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology
  • Case-Control Studies
  • China
  • DNA / analysis
  • DNA Methylation*
  • DNA Primers
  • Disease-Free Survival
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • MutS Homolog 2 Protein / blood*
  • MutS Homolog 2 Protein / genetics
  • Polymerase Chain Reaction
  • Predictive Value of Tests
  • Promoter Regions, Genetic
  • Prospective Studies

Substances

  • Biomarkers, Tumor
  • DNA Primers
  • DNA
  • MSH2 protein, human
  • MutS Homolog 2 Protein