Overexpression of p53 protein is not directly related to hepatitis B x protein expression and is associated with neoplastic progression in hepatocellular carcinomas rather than hepatic preneoplasia

p53 mutations and binding of p53 to hepatitis B virus (HBV) x protein (HBx) have been suggested as alternative mechanisms of development of hepatocell ular carcinomas (HCCs) in man, both processes resulting in intracellular ac cumulation of the protein which is detectable by immunohistochemical approa ches. We have examined p53 expression in 149 explanted human livers, includ ing 39 cases infected with HBV and 35 bearing HCC. p53 was demonstrated imm unohistochemically in 51% of HCC samples (18/35), localized mainly in fast growing poorly differentiated areas. Accumulation of mutant p53 was verifie d by immunoprecipitation in most of the positive HCC samples (14/15), imply ing occurrence of p53 mutations. No cells positive for p53 were found in 35 4 preneoplastic hepatocellular lesions examined. This indicates that p53 mu tation is associated with progression, rather than early development, of HC C in the low-aflatoxin B-1-exposed region. The intracellular distribution p atterns of p53 and HBx were different, with the former within nuclei and th e latter confined to cytoplasmic compartment. HBx did not coimmunoprecipita te with p53. These data indicate that p53-HBx binding is infrequent, if it really occurs, in HBV-infected human liver, and that it cannot be a common mechanism of HBV-associated hepatocarcinogenesis. In addition, p53 accumula tion was also observed in some parenchymal and ductular (oval) cells in cir rhotic livers and, more frequently, in fulminant hepatitis, being independe nt of HBx expression, and seemingly associated with the damage and/or regen eration of liver parenchyma, perhaps merely reflecting a cellular stress re sponse, (C) 2000 Elsevier Science B.V. All rights reserved.