Expression of p27KIP1 and p21WAF1/CIP1 in primary hepatocellular carcinoma: Clinicopathologic correlation and survival analysis

Abstract

To investigate the possible roles of p27KIP1 and p21WAF1/CIP1, inhibitors of cyclin-dependent kinases, in hepatocellular carcinoma (HCC), we examined p27KIP1 and p21WAF1/CIP1 expression in primary HCC with immunohistochemistry and Northern blot hybridization and correlated the results with clinicopathologic features and survival. With immunohistochemistry, positive staining for p27KIP1 and p21WAF1/CIP1 protein was found in 54.3% and 63.8% of HCCs, respectively. Both p27KIP1 and p21WAF1/CIP1 scores of the tumors were significantly higher than those of the corresponding nontumorous livers (P < .0001 and .009, respectively). Higher leveis of p27KIP1 were associated with a lower incidence of direct liver invasion (P = .021) and, less significantly, with a low incidence of multiple tumor nodules (P = .056). Patients whose tumors had higher p27KIP1 protein scores had longer disease-free survival (P = .011). For p21WAF1/CIP1 in contrast to the overexpression of the p21WAF1/CIP1 protein in HCC, the relative amounts of p21WAF1/CIP1 messenger RNA (mRNA) in the tumors were found to be reduced compared with those of the nontumorous livers (P = .039). In conclusion, p27KIP1 and p21WAF1/CIP1 proteins were frequently overexpressed in HCC. Longer disease-free survival rates were seen in patients whose tumors had higher p27KIP1 expression. The accumulation of p21WAF1/CIP protein in the presence of a reduced mRNA level suggests probable posttranslational protein stabilization, and the reduced transcription of p21WAF1/CIP may represent a form of dysfunction of cyclin-dependent kinase inhibitor involved in hepatocarcinogenesis. Copyright © 2001 by W.B. Saunders Company.