p21 Protein Expression and Cell Proliferation Activity in Human Multistep Hepatocarcinogenesis

p21 is a universal inhibitor of cyclin-dependent kinase (cdk) and of cell-cycle progression. p21 expression is variable according to the type of tissue and the pathologic condition. To study the role of p21 in the multistep hepatocarcinogenesis, the expression of p21, p53 and Ki-67 was investigated in 53 cases of inactive liver cirrhosis, 4 cases of low grade dysplastic nodules, 3 cases of high grade dysplastic nodules, 7 cases of early hepatocellular carcinomas (HCCs), 27 cases of small HCCs (3 cm). p21 expression was not detected in liver cirrhosis, low grade dysplastic nodules, high grade dysplastic nodules and early HCCs which were mitotically inactive. p21 expression was significantly increased in small HCCs and advanced HCCs which were mitotically active. p21 expression was significantly correlated with Ki-67 labelling indices. p53 protein was not expressed in liver cirrhosis, dysplastic nodules, and early HCCs. The expression of p53 protein was, however, significantly increased in small and advanced HCCs. The p21 expression was not correlated with p53 expression. Therefore, p21 is suggested to play a role in the mitotically active small and advanced HCCs, but not in the mitotically inactive lesion of dysplastic nodules and early HCC in multistep hepatocarcinogenesis. These findings suggest that homeostatic mechanism of growth control is not totally destroyed in HCC.ope