p16 expression in Barrett's esophagus and esophageal adenocarcinoma: association with genetic and epigenetic alterations.

Alteration of the p16 tumor suppressor gene has been implicated as a critical lesion in the molecular pathogenesis of esophageal adenocarcinoma. The aim of this study was to characterize the spectrum of p16 alterations in surgically resected esophageal tissues, comprising histologically normal esophageal squamous and gastric epithelia, premalignant Barrett's epithelia, and associated esophageal adenocarcinomas, and to explore associations between p16 mRNA expression and p16 mutations, deletions, promoter hypermethylation, p16 protein expression, and clinico-pathologic features for the same tissues. We have shown that while p16 mutations are uncommon (2%; 1/54), hypermethylation of the p16 promoter is detected in 43% (9/21) of histologically normal epithelia, in 77% (14/18) of associated Barrett's epithelia, and in 85% (18/21) of esophageal adenocarcinomas.