Expression of ras and c-myc oncoproteins and hepatitis B surface antigen in human liver disease

• Published in: Hepato-gastroenterology Vol. 40; no. 1; p. 37
• Main Authors: Tiniakos, D, Spandidos, D A, Yiagnisis, M, Tiniakos, G
• Format: Journal Article
• Language: English
• Published: Greece 01.02.1993
• Subjects: Female; Gene Expression; Hepatitis B - genetics; Hepatitis B - immunology; Hepatitis B - pathology; Hepatitis B Surface Antigens - genetics; Hepatitis B virus - genetics; Humans; Liver - immunology; Liver - pathology; Liver Cirrhosis - genetics; Liver Cirrhosis - immunology; Liver Cirrhosis - pathology; Male; Middle Aged; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins p21(ras) - genetics
• ISSN: 0172-6390

One of the major antecedent factors preceding the development of hepatocellular carcinoma is chronic hepatitis B virus infection. Also, recent molecular studies have shown that activation of c-oncogenes might be responsible for the malignant transformation in some cases of hepatocellular carcinoma. We used immunohistochemical methods to investigate the correlation of ras and c-myc oncogene expression with the presence of HBsAg in human liver disease. Our material consisted of 23 chronic active hepatitis B needle liver biopsies and surgical specimens from 11 cases of cirrhosis, 23 hepatocellular carcinoma and 10 normal adult livers. Direct, three-step and streptavidin-biotin-complex immunoperoxidase techniques using polyclonal (anti-HBsAg) and monoclonal antibodies (anti-ras p21, anti-myc p62), were performed. Normal liver tissues were negative for all antibodies used. In HBsAg+ chronic active hepatitis B cases enhancement of c-myc, and less frequently of ras oncogene expression, was a common observation. Increased myc p62 and ras p21 expression was a finding not restricted to HBsAg+hepatocytes, which occasionally were negative for oncoprotein immunostaining. All HBsAg-chronic active hepatitis B cases were negative for ras p21 and myc p62 specific staining. Cirrhotic livers showed more frequently enhanced c-myc expression. Most of the immunostained cells were negative for HBsAg. HBsAg- cases of hepatocellular carcinoma more often showed ras p21 than myc p62 overexpression. HBsAg+ hepatocellular carcinomas presented only ras p21-positive immunostaining, which was not detected in HBsAg+ hepatocytes. Our recent data supports the view that continued expression of HBsAg in human liver disease is not necessary for the enhancement of ras and c-myc oncogene expression.