Expression of Ki-67, transforming growth factor beta1, and B-cell lymphoma-leukemia-2 in liver tissue of patients with chronic liver diseases

J Gastroenterol Hepatol. 2006 Apr;21(4):700-10. doi: 10.1111/j.1440-1746.2006.04149.x.

Abstract

Background: The purpose of the present paper was to assess expression of proliferation, fibrosis and apoptosis markers in different phases of chronic liver diseases.

Methods: Sixty-six adults with chronic liver diseases (chronic hepatitis C, n = 48; chronic hepatitis B, n = 10; alcohol chronic liver disease, n = 8) treated at the Department of Infectious Diseases and Hepatology from 1999 to 2001, composed the study group. Liver biopsy specimens were used for immunohistochemical assessment of expression of Ki-67, transforming growth factor beta1 (TGF-beta1) and B-cell lymphoma-leukemia-2 (Bcl-2). Grade of liver inflammation and stage of fibrosis were evaluated according to the Scheuer scale.

Results: Expression of Ki-67 in hepatocytes was most intensive in patients with grade 2 and 3 inflammation. The expression in patients with grade 4 inflammation was low. The expression of Ki-67 in lymphocytes was most intensive in patients with grade 2 inflammation. Expression of TGF-beta1 in hepatocytes reached a maximum in patients with grade 2 or 3 inflammation and dropped in patients with grade 4 inflammation. There was a statistically significant correlation between stage of fibrosis and expression of TGF-beta1 in liver stromal cells. A very strong correlation was found between the expression of Bcl-2 in bile ductules epithelium and the grade of inflammation (P = 0.006). The expression of Bcl-2 in hepatocytes was observed only in patients with very intense liver inflammation (grade 3) and in patients with stage 3 or 4 fibrosis.

Conclusion: Processes of proliferation, fibrosis and apoptosis are not directly correlated to progression of liver disease. Expression of studied markers can be used for analysis of dynamics of these processes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis
  • Cell Proliferation
  • Chronic Disease
  • Gene Expression
  • Hepatocytes / metabolism*
  • Humans
  • Ki-67 Antigen / metabolism*
  • Liver / metabolism*
  • Liver Cirrhosis / metabolism
  • Liver Diseases / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Transforming Growth Factor beta / metabolism*
  • Transforming Growth Factor beta1

Substances

  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • TGFB1 protein, human
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1