Hepatitis B x antigen in hepatitis B virus carrier patients with liver cancer.

Formalin-fixed, paraffin-embedded specimens from 110 cases of primary hepatocellular carcinoma were stained for hepatitis B x antigen (HBxAg), hepatitis B surface antigen (HBsAg), and hepatitis B core antigen (HBcAg). Eighty-four % of these patients were HBxAg positive in their tumor cells. Among the 110 cases studied, 80 had adjacent nontumorous tissue in the same block, and 65 of these nontumorous liver tissues stained positive for HBxAg (81%). HBsAg was positive in 19% of cases within tumor tissue and 61% in surrounding nontumorous tissue. HBcAg was positive in 11% of cases within tumor tissue and 26% in surrounding nontumorous tissue. These findings show that HBxAg is a common marker in the liver of patients with hepatitis B virus (HBV)-associated primary hepatocellular carcinoma and that it is closely associated with tumor cells in these individuals. In addition, the finding of HBxAg in the absence of detectable HBsAg and HBcAg in the liver tissues of many HBsAg carriers suggests that HBxAg could be expressed independent of HBV replication and implies that the synthesis of this antigen may be directed from integrated HBV DNA templates. The finding of HBxAg in the nucleus of hepatocytes from primary hepatocellular carcinoma patients with dysplasia, combined with the known trans-activating properties of HBxAg, implies that HBxAg plays one or more important roles in hepatocarcinogenesis. The finding of HBxAg in bile duct epithelium and cholangiocarcinoma tissues is compatible with the hypothesis that HBV may contribute to this other primary tumor type in the liver. Together, these results further implicate HBxAg in the pathogenesis of primary liver cancers.