Promoter region hypermethylation of cell cycle related gene in hepatocarcinogenesis

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Inactivation of the p16 (INK4A) tumor suppressor gene by promoter region hypermethylation has been shown not only in many types of tumor, including hepatocellular carcinoma (HCC). Our previous study suggested that methylation of the p16 promoter region and the resulting loss of p16 protein expression are early events in a subset of hepatocarcinogenesis.The objective of this study was to determine the usefulness of the loss of p16 protein expression and the methylation of the p16 promoter region as a prognostic factor for hepatocarcinogenesis.In univariate analysis, loss of p16 protein was significantly correlated with hepatocarcinogenesis (p<0.05). In multivariate analysis, sex, age, fibrosis and loss of p16 protein expression retained independent prognostic significance.Our results suggest that the loss of p16 protein expression are early events in a subset of hepatocarcinogenesis and that their detection is useful to follow up chronic hepatitis patients with a high risk for developing HCC, such as those with HBV or HCV infections.