A quantitative gene expression study suggests a role for angiopoietins in focal nodular hyperplasia

Gastroenterology. 2003 Mar;124(3):651-9. doi: 10.1053/gast.2003.50104.


Background and aims: Although the pathogenesis of focal nodular hyperplasia (FNH) of the liver remains unclear, a vascular mechanism has been suspected. To gain insight into the pathogenesis of FNH, we performed a large-scale quantitative study of gene expression in FNH.

Methods: Quantitative expression level of 209 selected genes was assessed using real-time reverse-transcription polymerase chain reaction in 14 cases of FNH and compared with their expression level in 13 cases of liver cirrhosis, 4 adenomas, and 15 hepatocellular carcinomas.

Results: Among the 7 genes, the expression of which was significantly up-regulated or down-regulated in FNH, the most informative markers for the diagnosis of FNH as assessed using the receiving operative curve and area under the curve (AUC) were angiopoietin-1 (Ang-1; AUC, 0.82) and angiopoietin-2 (Ang-2; AUC, 0.80). These 2 genes are involved in the regulation of vasculogenesis. In FNH, Ang-1 was significantly up-regulated, Ang-2 was down-regulated, and the Ang-1/Ang-2 ratio was highly and specifically increased in FNH compared with normal liver or other groups of lesions (FNH, 15.2-fold increase; HCC, 2.78; adenoma, 2.28; cirrhosis, 1.92; P < 0.01 for FNH vs. all groups, analysis of variance). Tie-2 messenger RNA, the receptor of Ang-1 and Ang-2, was detected at the same level in FNH as in normal liver. Ang-1 protein was detected on Western blot of FNH and expressed by endothelial cells of dystrophic vessels and sinusoids as shown by immunohistochemistry.

Conclusions: A specific increase of Ang-1/Ang-2 ratio in FNH, in the presence of the functional Tie-2 receptor, might be involved in the formation of hyperplastic and dystrophic vessels of FNH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inducing Agents / genetics
  • Angiogenesis Inducing Agents / metabolism*
  • Angiopoietin-1
  • Angiopoietin-2
  • Carcinoma, Hepatocellular / genetics
  • Child
  • Child, Preschool
  • Female
  • Focal Nodular Hyperplasia / genetics*
  • Focal Nodular Hyperplasia / physiopathology*
  • Gene Expression
  • Gene Expression Profiling*
  • Humans
  • Immunohistochemistry
  • Liver Cirrhosis / genetics
  • Liver Neoplasms / genetics
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Middle Aged
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor, TIE-2


  • Angiogenesis Inducing Agents
  • Angiopoietin-1
  • Angiopoietin-2
  • Membrane Glycoproteins
  • Receptor Protein-Tyrosine Kinases
  • Receptor, TIE-2