Methylation of the p16 tumor suppressor gene in Korean patients with colon cancer and adenoma

Kim, Do Ha; Cho, Mong; Kim, Dae Hyun; Joo, Kwang Ro; Park, Neung Hwa; Yang, Ung Suk

Abstract

BACKGROUND: De novo methylation and transcriptional silencing of p16 gene is one of the main pathways in inactivation of p16 gene in colon neoplasm. But there has been no study about that in Korea yet. The aims of this study were to determine p16 methylation status and its association with clinicopathologic parameters and stage of colon cancers and adenomas in patients of Korea.
METHODS
We examined p16 methylation of sixty primary colon cancer tissues and thirty colon adenoma tissues using methylation specific PCR after bisulfite modification of the DNA samples.
RESULTS
In colon cancer group, 30 patients were male and the others were female, and the average age was 59.7+/-12.5 years. Three cases were in Dukes' stage A, 24 in B, 26 in C, and 7 in D respectively. p16 gene was methylated in 20% (12 of 60) of colon cancers. There was no significant correlation between methylation status of p16 gene and clinicopathologic variables of colon cancers including patient's age, sex, tumor location, size, and differentiation. In Dukes' stage C and D, methylation was positive in 24.2% (8/33 cases) comparing 14.8% (4/27 cases) in Dukes' A and B, but there was no significant difference statistically (p=0.52). In colon adenoma group, there were 15 simple adenomas, and 15 advanced adenomas (>or=1cm, including villous component, or high grade dysplasia). The p16 gene was methylated in 16.7% (5 of 30) of colon adenomas; in 3 cases of simple adenoma and in 2 cases of advanced adenoma. There was no significant correlation between p16 methylation status and clinicopathological variables in colon adenoma.
CONCLUSION
The p16 gene was methylated in 20% of colon cancers and 16.7% of colon adenomas in the present series, suggesting that the methylation of p16 tumor suppressor gene might be expressed in similar rate in colon cancer/adenoma in Korea, and play a role in colorectal tumorigenesis in its early stage.