p16 gene methylation and its protein expression in primary hepatocellular carcinoma

Objective To investigate p16 gene methylation and its protein expression in the pathogenesis and progression of hepatocellular carcinoma (HCC).Methods In 10 fresh HCC specimens and 33 HCC paraffin block samples, p16 gene methylation were detected by by MS_PCR and p16 protein expression detected by immunohistochemistry(IHC).Results Loss of p16 protein expression was found in 28 of 43(65.1%) HCCs, while in 3 of 26 corresponding paracancerous liver tissues. The p16 protein loss rate in HCCs was significantly higher than that in paracancerous tissues (P0.01). The loss rate of p16 protein in gradesⅠand Ⅱ was significantly lower than that in grade Ⅲ(P0.05). Through MS-PCR, p16 gene methylation was found in 19 protein loss HCCs (44.2%) and in 1 of 10 paracancerous liver tissues. The methylation rate in HCCs was significantly higher than that in paracancerous tissues (P0.05). No gene methylation was found in cases expressing p16 protein. p16 gene methylation was closely related to p16 protein loss in HCC (P0.01). There were significant differences between the methylation rates of three HCC grades (P0.05).Conclusion Loss of p16 protein expression and p16 gene methylation are closely related to the carcinogenesis of HCC. p16 might be a marker in diagnosing malignant degree in HCC. Gene methylation is the primary inactive mechanism of p16 and there is close relationship between the differentiation and methylation in HCC.