Objective: To identify CpG island hypermethylation of 5'region of hMLH1 promotor and to explore its relationship to microsatellite instability(MSI)in sporadic colorectal carcinoma.
Methods: Forty-one pairs of tissue specimens (normal and cancer) were collected from 41 patients with colorectal cancer. Hypermethylation of hMLH1 promoter was detected by methylation specific PCR; the relationship between methylation and clinicopathological features was analyzed. Combined with BAT25 and BAT26, the MSI status was detected using an automated fluorescent DNA sequencer.
Results: Hypermethylation of hMLH1 promoter was detected in 75.6 % (31/41) of samples. Mean age of unmethylation cases (49.2 y) was significantly younger than that of methylation cases (63.6 y) (P<0.05), but there were no differences between two groups in other clinicopathological features. MSI was detected in 43.9 % samples (18/41); hypermethylation of hMLH1 promoter was detected in 94.4 % (17/18) of MSI(+) samples, which was higher than that in MSI(-) samples (60.9 %,14/23, P<0.05).
Conclusion: Age-related hypermethylation is generally found in patients with sporadic colorectal cancers, which may cause MSI and might be the mechanism in the development of colorectal cancer of elderly people.