Integrity of p53 in hepatitis B x antigen-positive and -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 hepatitis B virus-encoded X antigen (HBxAg) binds to and inactivates wild-type p53. Hence, experiments were designed to test the hypothesis that there is a low frequency of p53 mutations in HBxAg-positive HCC. HBxAg and p53 were assayed by immunohistochemistry (IHC) in HCC and nontumor liver from 16 Chinese patients, half of whom were hepatitis B surface antigen carriers. HBxAg was detectable in tumor and/or nontumor cells from all patients by IHC; six of these samples also had detectable p53. To determine whether p53 detection by IHC, and hence stabilization, is associated with mutation, sequencing of p53 exons 5-8 was performed with each patient sample. Wild-type sequences were found in 13 of 16 HBxAg-positive cases (81%). Hence, HBxAg is a common marker of HCC that correlates with the persistence of wild-type p53 among both carriers and noncarriers. The low frequency of p53 mutations in HCC in these patients implies that p53 inactivation may occur predominantly by complex formation with HBxAg.
Greenblatt
M S
MS
Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Feitelson
M A
MA
Zhu
M
M
Bennett
W P
WP
Welsh
J A
JA
Jones
R
R
Borkowski
A
A
Harris
C C
CC
D006528:Carcinoma, Hepatocellular / Q000209:etiology*; D006511:Hepatitis B Antigens / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000209:etiology*; D009154:Mutation; D015534:Trans-Activators / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D054334:Viral Regulatory and Accessory Proteins
D006511:Hepatitis B Antigens; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein