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Objective: Aberrant expression of DNA repair genes such as hMLH1 and MSH2 has been shown to contribute to carcinogenesis of lung and gastrointenstinal cancers. Further, promoter hypermethylation is believed to be one of the major mechanisms that leads to gene silencing of a variety of tumor suppressor and DNA repair genes in human cancers. To investigate whether promoter hypermethylation is involved in silencing of gene expression of hMLH1 and whether its protein expression, along with MSH2 are related with squamous cell carcinoma (SCC) of the esophagus.
Methods: We analyzed promoter methylation status of hMLH1 using methylation-specific polymerase chain reaction (MSP) and immunostainig for hMLH1 and MSH2 in 60 resected tumor specimens. Results are correlated with clinicopathologic parameters using Spearman correlation test. Concordance analysis was performed for methylation of hMLH1 and its protein expression.
Results: Loss of hMLH1 and MSH2 expression was found in 40 (66%) and 36 (60%) in 60 resected specimens. Protein expression of hMLH1 correlated well with tumor staging and depth of tumor invasion (T) but not nodal involvement or distant metastasis, whereas MSH2 did not show correlation with neither of these parameters. A concordance rate of 80% was present between protein expression of hMLH1 and its gene methylation.
Conclusions: These results suggest that: 1. Aberrant protein expression of hMLH1 and MSH2 is associated with tumorigenesis of esophageal SCC, 2. As compared with MSH2, hMLH1 expression may serve as a better prognostic predictor for resected SCC of the esophagus, 3. Promoter hypermethylation is at least one of the mechanisms responsible for silencing of hMLH1 expression.

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