Promoter methylation of the hMLH1 gene and protein expression of human mutL homolog 1 and human mutS homolog 2 in resected esophageal squamous cell carcinoma

Ching Tzao, Han Sui Hsu, Guang Huan Sun, Hsiou Lei Lai, Yi Ching Wang, Ho Jui Tung, Cheng Ping Yu, Yeung Leung Cheng, Shih Chun Lee

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Objective: Aberrant expression of mismatch repair genes, such as human mutL homolog 1 (hMLH1) and human mutS homolog 2 (hMSH2), are common in some human cancers, and promoter methylation is believed to inactivate expression of hMLH1. We investigated whether promoter methylation is involved in loss of hMLH1 protein and whether aberrant expression of hMLH1 and hMSH2 protein is related to prognosis after resection for esophageal squamous cell cancer. Methods: We analyzed promoter methylation of hMLH1 using methylation-specific polymerase chain reaction and hMLH1 and hMSH2 protein by using immunohistochemistry in 60 resected tumor specimens. The Pearson χ2 test was used to compare expression of hMLH1 and hMSH2 protein among patients with different clinicopathologic parameters. Concordance analysis was performed between hMLH1 methylation and its protein expression. Results: Loss of hMLH1 and hMSH2 protein was found in 43 (72%) and 39 (65%, P = .06) of 60 resected specimens, respectively. hMLH1 protein correlated well with tumor staging (P <.0001), depth of tumor invasion (P = .008), and nodal involvement (P <.0001) but not with distant metastasis, whereas hMSH2 did not show correlation with any of these parameters. A concordance rate of 83.3% was present between expression of hMLH1 protein and its promoter methylation (P <.001). Conclusions: Aberrant expression of hMLH1 and hMSH2 protein is frequently associated with the presence of esophageal squamous cell carcinoma, and expression of hMLH1 protein is a better prognostic predictor than is expression of hMSH2 protein. Promoter methylation is one of the mechanisms responsible for loss of hMLH1 protein in esophageal squamous cell cancer.

Original languageEnglish
JournalJournal of Thoracic and Cardiovascular Surgery
Volume130
Issue number5
DOIs
Publication statusPublished - Nov 2005
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

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