Regular Article

British Journal of Cancer (2000) 83, 50–55. doi:10.1054/bjoc.2000.1310 www.bjcancer.com
Published online 6 June 2000

Reduced p21WAF1/CIP1 protein expression is predominantly related to altered p53 in hepatocellular carcinomas

Y-Z Shi1, A-M Hui1, T Takayama1, X Li1, X Cui1 and M Makuuchi1

1Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo0ku, Tokyo 113-0033, Japan

Received 14 July 1999; Revised 14 February 2000; Accepted 24 February 2000.

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Abstract

To investigate the relationship between the expression of p21WAF1/CIP1 protein and p53 status and the possible role of the two proteins in hepatocellular carcinomas (HCCs), we examined the expression of p21WAF1/CIP1 and p53 immunohistochemically in 81 tumours from 65 patients with hepatocellular carcinoma. p21WAF1/CIP1 protein was absent from 59 of 81 tumours (72.8%), and altered p53 expression was found in 43 (53.1%). p21WAF1/CIP1 expression was significantly associated with p53 status (P= 0.0008); 38 of 59 tumours lacking p21WAF1/CIP1 protein were accompanied by altered p53 expression. Further analyses showed that p21WAF1/CIP1 expression was inversely correlated with p53 expression in hepatitis C virus (HCV)-related HCCs, but not in HBV-related hepatocellular carcinomas and hepatocellular carcinomas without viral infection. All 11 tumours with intrahepatic metastasis showed altered p21WAF1/CIP1 or p53 expression. In contrast, no intrahepatic metastasis was found in any of the 17 tumours without abnormal expression of either of the two proteins. These results suggest that: (1) different modes of p21WAF1/CIP1 regulation are involved in HCCs differing in their hepatitis viral infection status, and p21WAF1/CIP1 expression appears to be predominantly related to altered p53 in HCV-related HCCs; (2) disruption of the p53–p21WAF1/CIP1 cell- cycle-regulating pathway may contribute to malignant progression of HCC. © 2000 Cancer Research Campaign

Keywords:

p21WAF1/CIP1, p53, hepatocellular carcinoma

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