A lack of direct role of hepatitis B virus in the activation of ras and c‐myc oncogenes in human hepatocellular carcinogenesis

Abstract

This study was performed to determine the relationship of the activation of ras and c‐myc oncogenes in human hepatocellular carcinoma to the hepatitis B virus gene expression or the presence of hepatitis B virus DNA/RNA at the cellular level. This was done using immunocytochemical analysis with two different antibodies on serial sections. In addition, immunocytochemical assay for the detection of ras p21 or c‐myc protein was performed in combination with in situ hybridization for hepatitis B virus DNA/RNA using 35S‐labeled hepatitis B virus DNA as a probe. Investigation of a total of 14 paired human hepatocellular carcinoma and adjacent nontumorous hepatic tissues revealed enhanced expression of ras p21 in one human hepatocellular carcinoma whereas c‐myc protein was found in one paired human hepatocellular carcinoma and nontumorous tissue of the same patient. Only a small proportion of human hepatocellular carcinoma cells or hepatocytes among a large number of cells on a given section showed enhanced expression, and the distribution of the oncogene product‐expressing cells was focal. However, the cells over‐expressing these oncogenes did not show hepatitis B surface antigen in the serial sections. Furthermore, the combined immunocytochemical and in situ hybridization assays revealed that human hepatocellular carcinoma cells overexpressing ras p21 did not show hepatitis B virus DNA/RNA, whereas some human hepatocellular carcinoma cells and nontumorous hepatocytes located away from the foci of oncogene‐expressing cells gave positive signals. These findings suggest that continued expression of HBsAg or the presence of hepatitis B virus DNA/RNA in a given human hepatocellular carcinoma cell is not necessary for enhanced expression of ras or c‐myc proteins. We conclude that HBsAg expression or hepatitis B virus DNA/RNA may not have a direct role in the activation of ras and c‐myc oncogenes. Copyright © 1988 American Association for the Study of Liver Diseases