Localization of hepatitis B surface and core antigens in human hepatocellular carcinoma by immunoperoxidase methods. Replication of complete virions of carcinoma cells

Abstract

The localization of hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) was investigated by an indirect immunoperoxidase method in formalin-fixed, paraffin-embedded liver specimens obtained from 95 Japanese patients with hepatocellular carcinomas. Routine and immune electron microscopic examinations were done in one case. The correlation between expression of hepatitis B virus antigens in the tissue and serum hepatitis B e antigen (HBeAg)/antibody to HBeAg (anti-HBe) status was examined. Hepatitis B surface antigen was detected in the cytoplasm of noncarcinomatous hepatocytes in 28 (29.5%) cases and of carcinoma cells in 11 (11.6%) cases. Hepatitis B core antigen was stained in noncarcinomatous hepatocytes in 13 (13.7%) cases and in carcinoma cells in 4 (4.2%) cases. Hepatitis B core antigen was present mainly in the nuclei, and all HBcAg-positive cases were positive for HBsAg. The routine electron microscopic examination revealed many round particles, 25 to 30 nm in diameter both in the nuclei and in the cytoplasm, and larger particles, 40 to 45 nm in diameter in the cytoplasm of carcinoma cells. Both types of particles had reaction products of HBcAg by immunoelectron microscopic study. Therefore, it was confirmed that the former were cores and the latter were Dane particles. There was a tendency that HBeAg-seropositive cases showed localization of HBcAg in the noncarcinomatous tissue. Among four cases with positive HBcAg in carcinoma cells, two were positive for HBeAg, one was positive for anti-HBe, and the other was negative both for HBeAg and anti-HBe in the sera. The data suggested occasional production of complete hepatitis B viruses of carcinoma cells in anti-HBe-positive as well as in HBeAg-positive hepatocellular carcinomas.