Hypermethylation of the CDKN2/p16 promoter during neoplastic progression in Barrett's esophagus

Background & Aims: Inactivation of the CDKN2/p16(INK4A) tumor-suppressor ge ne is one of the most frequent genetic alterations in human malignancies. I n esophageal adenocarcinomas, mutations of the p16 gene or homozygous delet ions of the gene locus 9p21 are rare. This study investigated whether p16 p romoter hypermethylation is an alternative mechanism for p16 gene inactivat ion during neoplastic progression in Barrett's esophagus. Methods: A methyl ation-specific polymerase chain reaction protocol was applied. A total of 9 5 specimens from 14 patients with Barrett's esophagus were analyzed longitu dinally. The p16 promoter status was compared with histomorphological findi ngs. Results: p16 promoter hypermethylation was detected in 9 of the 10 pat ients who had displayed dysplasia at some time during surveillance, whereas none of the patients who had not displayed dysplasia during surveillance h ad p16 promoter hypermethylation. p16 promoter hypermethylation was detecte d in 3% (2 of 67) of the samples without dysplasia, 60% (3 of 5) of the sam ples with lesions indefinite for dysplasia, 55.6% (10 of 18) of the specime ns with low-grade dysplasia, and 75% (3 of 4) of the specimens with high-gr ade dysplasia. Conclusions: These data suggest that p16 promoter hypermethy lation is a common mechanism of p16 gene inactivation during neoplastic pro gression in Barrett's esophagus.