Frequent Loss Of P19(Ink4d) Expression In Hepatocellular Carcinoma: Relationship To Tumor Differentiation And Patient Survival

p19(INK4D) belongs to the family of cyclin-dependent kinase inhibitors (CdkIs) that target the cyclin-dependent kinases and inhibit their catalytic activity. The role of p19(INK4D) in cell cycle progression in hepatocellular carcinoma (HCC) is poorly characterized. The aim of this study was to examine the expression of p19(INK4D) in various liver diseases including HCC and to assess its clinical significance in HCC. We examined the expression of p19(INK4D) by immunohistochemistry in 81 cases of various liver diseases, including 51 HCCs. We analyzed the relationship among p19(INK4D) expression in HCC in combination with histopathological stage, differentiation, several histopathological factors of possible prognostic value and patient survival. Immunohistochemical analysis revealed the frequent loss of p19(INK4D) expression consistent with the differentiation of HCC. The loss of p19(INK4D) expression was shown to be associated with a poor prognosis by analyzing clinicopathological features. In conclusion, we found that loss of p19(INK4D) protein was frequent in HCC, especially in poorly differentiated HCC, suggesting that p19(INK4D) may play a role in the differentiation of HCC. Furthermore, expression of p19(INK4D) may be an effective predictor of clinical behavior in HCC, and therefore, a new prognostic marker for HCC.