PROGNOSTIC SIGNIFICANCE OF p21 AND p53 EXPRESSION IN HEPATOCELLULAR CARCINOMA

Abstract

The cyclin-dependent kinase inhibitor p21Waf1/Cip1(p21), which can be transcriptionally activated by p53-dependent and -independent manners, functions to block cell cycle progression. In this study, we analyzed the expression of p21, p53 and proliferating cell nuclear antigen (PCNA) in 85 patients with hepatocellular carcinoma (HCC) by inmiunohistochemistry, and examined whether expression of these proteins was related to prognosis in patients with HCC. In HCC, p21 positive tumors significantly showed high PCNA LI and small size, compared with p21 negative tumors. No relationship between p21 and p53 expression was detected. A multivariate Cox model analysis revealed p21, p53 expression and PCNA LI as independent prognostic factors (p=0.0059, p=0.0004, and p=0.0165, respectively). Furthermore, p21 expression significantly correlated with low recurrence rate in the p53 negative cases (p=0.020) and related to a good outcome in the high PCNA LI cases (p=0.056). Accordingly, the analysis of p21, p53 and PCNA could play an important role in early detection of intrahepatic recurrence and might contribute to improvement of the prognostic characterization.