INTEGRITY OF P53 IN HEPATITIS-B X-ANTIGEN-POSITIVE AND X-ANTIGEN-NEGATIVE HEPATOCELLULAR CARCINOMAS

Inactivation of the tumor suppressor p53 seems to be important to the pathogenesis of hepatocellular carcinoma (HCC) associated with chronic hepatitis B virus infection, Although this inactivation may be due to mutations in the p53 gene, recent evidence suggests that the hepatiti s B virus-encoded X antigen (HBxAg) binds to and inactivates wild-type p53, Hence, experiments were designed to test the hypothesis that the re is a low frequency of p53 mutations in HBxAg-positive HCC, HBxAg an d p53 were assayed by immunohistochemistry (IHC) in HCC and nontumor l iver from 16 Chinese patients, half of whom were hepatitis B surface a ntigen carriers, HBxAg was detectable in tumor and/or nontumor cells f rom all patients by IHC; six of these samples also had detectable p53, To determine whether p53 detection by MC, and hence stabilization, is associated with mutation, sequencing of p53 exons 5-8 was performed w ith each patient sample, Wild-type sequences were found in 13 of 16 KB xAg-positive cases (81%), Hence, HBxAg is a common marker of HCC that correlates with the persistence of wild-type p53 among both carriers a nd noncarriers, The low frequency of p53 mutations in HCC in these pat ients implies that p53 inactivation may occur predominantly by complex formation with HBxAg.