HYPERMETHYLATION OF THE P16(INK4A) PROMOTER IN COLECTOMY SPECIMENS OFPATIENTS WITH LONG-STANDING AND EXTENSIVE ULCERATIVE-COLITIS

Functional inactivation of the p16(INK4a) gene has been reported to he involved in the development of a variety of human malignancies, Recen t evidence shows that transcriptional silencing as a consequence of hy permethylation of CpG islands is the predominant mechanism of p16(INK4 a) gene inactivation in sporadic colon cancer. This study sought to id entify the significance of p16(INK4a) methylation in the colonic epith elium of patients with long-standing ulcerative colitis, A total of 89 tissue samples was retrieved from three colectomy specimens. A methyl ation-specific PCR assay was applied. The methylation status was compa red with histological findings and the flow cytometrically determined DNA index, Hypermethylation of the p16(INK4a) promoter region was dete cted in 12.7% of samples that were negative for dysplasia, However, 70 .0% of samples with dysplasia and all of the samples with carcinomatou s lesions revealed hypermethylation, Hypermethylation of the p16(INK4a ) gene promoter was detected already in 40% of specimens with lesions indefinite for dysplasia and in 13.7% of samples with exclusively dipl oid cell populations. These results suggest that hypermethylation of t he p16(INK4a) promoter region is a frequent and early occurring event during the process of neoplastic progression in ulcerative colitis.