Correlation of laterally spreading type and JC virus with methylator phenotype status in colorectal adenoma

Abstract

Accurate frequencies of CpG island methylator phenotype (CIMP) have not been determined for laterally spreading tumors (LSTs) and other flat-type colorectal adenomas, and the role of JC virus T-antigen (T-Ag) in these tumors is unclear. We used MethyLight assay to analyze the relationship between CIMP status and clinicopathologic characteristics in tissue from 72 LST of granular-type (LST-G), 35 LST of nongranular-type (LST-NG), 54 protruded-type adenomas, and 89 colorectal cancers. We also investigated the relationship between CIMP status and T-Ag by immunohistochemistry. With the use of 5 markers for CIMP status, tumors were classified as CIMP-high (> or = 4/5 methylated promoters), CIMP-low (1/5 to 3/5 methylated promoters), or CIMP-0 (no methylated promoters). The proportion classified as CIMP-0 status was 5.6% for protruded-type adenoma, 17.1% for LST-NG, and 29.2% for LST-G (LST-G versus protruded-type adenoma, P = .001). CIMP-low status was established for 62.5% of LST-G, 74.3% of LST-NG, and 81.5% of protruded-type adenomas. CIMP-high status was established for 8.3% of LST-G, 8.6% of LST-NG, and 12.9% of protruded-type adenomas. The proportions of CIMP-low and CIMP-high status were not significantly different between the 3 groups. Multiple logistic analysis showed that LST-G appearance was the only significant factor for identifying CIMP-0 status. BRAF mutation was the only significant factor for identifying CIMP-high status. T-Ag expression increased with CIMP status and was not associated with macroscopic appearance. In conclusion, among colorectal adenomas, CIMP-high status was determined by BRAF mutation and not by macroscopic type, unlike CIMP-0. JC virus T-Ag may be important in determining methylator phenotype.