Stool methylation-specific polymerase chain reaction assay for the detection of colorectal neoplasia in Korean patients

PURPOSE: To investigate the feasibility of detecting hypermethylation in stool samples as a noninvasive screening tool for colorectal cancer and precancerous lesions, we evaluated the hypermethylation of three genes in the stool samples of patients with colorectal cancer, patients with colorectal adenomas, and healthy control subjects. METHODS: Stool samples were obtained from 37 endoscopically diagnosed healthy controls, 52 patients with adenomas, and 60 patients with colorectal cancer. The methylation status of the methylguanine DNA methyltransferase, human Mut L homolog-1, and vimentin promoter in bisulfite-modified DNA was investigated in a blinded manner by methylation-specific polymerase chain reaction with primer pairs designed to amplify specifically the methylated or unmethylated alleles. RESULTS: The methylated methylguanine DNA methyltransferase, human Mut L homolog-1, and vimentin were detected in 51.7%, 30.0%, and 38.3% of colorectal cancer, and in 36.5%, 11.%, and 15.4% of colorectal adenomas, respectively. The sensitivities of the combined study, using three markers for the detection of colorectal cancer and colorectal adenomas, were 75.0% and 59.6%. The specificity was 86.5%. CONCLUSION: Our results have demonstrated that the promoter hypermethylation for methylguanine DNA methyltransferase, human Mut L homolog-1, and vimentin in stool samples is a feasible epigenetic marker that is a sensitive, specific, and noninvasive alternative for colorectal cancer screening. This method of screening for colorectal cancer may be useful for patients that decline screening because of fear or inconvenience.