p53 and p21WAF1/CIP1 in hepatitis B virus related hepatocarcinogenesis.

ABSTRACT

BACKGROUND/AIMS: This study was undertaken to determine the expression p21WAF1/CIP1 and p53, the main regulator of G1 restriction point, in hepatitis B virus related hepatocarcinogenesis and their role in regulation of cell dynamics. METHODOLOGY: Immunohistochemistry for p21WAF1/CIP1, p53 and Ki-67 and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling were preformed in 8 low grade dysplastic nodules, 7 high grade dysplastic nodules, 58 hepatocellular carcinomas, and 62 chronic hepatitis/cirrhosis. In 33 hepatocellular carcinomas with fresh frozen tissue, p21WAF1/CIP1 mRNA was studied by reverse transcriptase polymerase chain reaction. RESULTS: Immunostaining for p21WAF1/CIP1 and p53 was positive in 28% and 38% of hepatocellular carcinomas and higher in poorly differentiated hepatocellular carcinomas, whereas it was negative in all of chronic hepatitis/cirrhosis and dysplastic nodules. In hepatocellular carcinomas with p21WAF1/CIP1 mRNA amplified, 31% showed the protein expression indicating post-transcriptional regulation. The rate of apoptosis and proliferation showed significant correlation with p53 status, however not with p21WAF1/CIP1 in hepatocellular carcinomas. Induction of p21WAF1/CIP1 was regulated by both p53 dependent and independent pathway. CONCLUSIONS: In hepatitis B virus related hepatocarcinogenesis, p21WAF1/CIP1 and p53 are suggested to be involved in late stage of tumor progression rather than in early stage of dysplastic nodules and p53 is considered to be the main regulator of the cell dynamics.