Microsatellite instability analysis and its correlation with hMLH1 repair gene hypermethylation status in esophageal pathologies including cancers

Abstract

Cancer development is associated with genetic instability. Identification of specific loci altered during carcinogenesis in a particular tissue gives scope for early detection and predicting the progressive nature of the tissue pathology. Instability at microsatellite loci is widely attributed to mismatch repair errors due to epigenetic alterations. Using three dinucleotide markers, D3S1313, D9S171, D17S250 and two mononucleotide markers BAT25, BATRII, we evaluated MSI in 97 cases enrolled for endoscopy of upper GI tract with symptoms of dyspepsia, reflux or dysphagia. We aimed at evaluating markers that reflect instability in esophageal malignancies, examine the prevalence of MSI in cancers and other pathologies of the esophagus, and determine the methylation status of hMLH1 gene in relation to MSI. 42% (21/50) cancers and 15.4%(2/13) precancers exhibited MSI where 85.7% cancers and 50% precancers with MSI, showed a hypermethylated hMLH1 promoter. Increased number of cases with repair gene methylation were seen with increasing severity of the esophageal pathology suggesting epigenetic progression parallels histologic changes. BAT25 and D3S1313 markers exhibited instability frequently and cases with MSI using these markers showed an abnormal hMLH1 promoter. Thus these markers were useful in identifying the mismatch repair phenotype. These two markers may be useful to screen cases for early cancer related changes, after validation on a larger sample.