Expression of p27(KIP1) and p21(WAF1/CIP1) in primary hepatocellular carcinoma: Clinicopathologic correlation and survival analysis

To investigate the possible roles of p27(KIP1) and p21(WAF1/CIP1), inhibito rs of cyclin-dependent kinases, in hepatocellular carcinoma (HCC), we exami ned p27(KIP1) and p21(WAF1/CIP1) expression in primary HCC with immunohisto chemistry and Northern blot hybridization and correlated the results with c linicopathologic features and survival. With immunohistochemistry, positive staining for p27(KIP1) and p21(WAF1/CIP1) protein was found in 54.3% and 6 3.8% of HCCs, respectively. Both p27(KIP1) and p21(WAF1/CIP1) scores of the tumors were significantly higher than those of the corresponding nontumoro us livers (P <.0001 and.009, respectively). Higher levels of p27(KIP1) were associated with a lower incidence of direct liver invasion (P = .021) and, less significantly, with a low incidence of multiple tumor nodules (P = .0 56). Patients whose humors had higher p27(KIP1) protein scores had longer d isease-free survival (P = .011). For p21(WAF1/CIP1), in contrast to the ove rexpression of the p21(WAF1/CIP1) protein in HCC, the relative amounts of p 21(WAF1/CIP1) messenger RNA (mRNA) in the tumors were found to be reduced c ompared with those of the nontumorous livers (P = .039). In conclusion, p27 (KIP1) and p21(WAF1/CIP1) proteins were frequently overexpressed in HCC. Lo nger disease-free survival rates were seen in patients whose tumors had hig her p27(KIP1) expression. The accumulation of p21(WAF1/CIP) protein in the presence of a reduced mRNA level suggests probable posttranslational protei n stabilization, and the reduced transcription of p21(WAF1/CIP) may represe nt a form of dysfunction of cyclin-dependent kinase inhibitor involved in h epatocarcinogenesis. HUM PATHOL 32:778-784. (C) 2001 by W.B. Saunders Compa ny.