Distinct Expressions of TGF-a among Chronic Hepatitis, Liver Cirrhosis, and Hepatocellular Carcinoma

Yoo, Byeong Moo; Park, Sung Soo; Lee, Dong Hoo; Lee, Jung Dal

Abstract

BACKGROUND/AIMS
Transforming growth factor-a(TGF-a) is a polypeptide cytokine related to cell proliferation and transformation. TGF-a binds to EGF receptor and stimulating DNA synthesis in liver cell. The hepatitis B virus (HBV) by itself is also believed to play a role in the hepatic carcinogenesis. Recently, it was reported that TGF-a and HBV were synergistic in action with rapid appearance of hepatocelluar carcinoma in bitransgenic mice. Although TGF- a is thought to play an important role in hepatocarcinogenesis, its expression during the natural history of HBV hepatitis was poorly understood. This investigation was performed to elucidate the dynamic changes and istinct immunohistochemical staining patterns in the course of chronic HBV hepatitis with specific reference to hepatocelluar carcinoma and to explain the role of TGF-a in the pathogenesis of hepatocelluar carcinoma.
MATERIALS/METHODS
Employing TGF-a monoclonal antibody, signal detection was carried out by peroxidase-conjugated streptavidin in deparaffinized liver tissue sections taken from HBsAg positive patients. All of the liver tissue sections were proven HBV DNA positive by in situ hybridization. Immunohistochemical staining was performed in the tissue sections obtained from four normal controls, six from patients with chronic persistent hepatitis, five with chronic active hepatitis, eight with liver cirrhosis and eleven with hepatocellular carcinoma.
RESULTS
The patterns of TGF-a immunoreactivity were cytoplasmic-grain types in normal controls and chronic persistent hepatitis, honeycomb types in chronic active hepatitis, occasional cytoplasmic-flooding types in liver cirrhosis, and cytoplasmic-grape types in hepatocellular carcinoma. A Shapiro-Wilk W test for frequency table analysis for the expression of TGF-a in these different disease groups was statistically significant.
CONCLUSION
These data suggest that step-wise distinct expression of TGF-a enhancement in HBV associated chranic liver diseases which eventually resulted in the development of hepatocellular carcinoma were conceivably due to dysregulation of liver cell cycles by both HBV and TGF-a during the persistent repetition of cell cycles.