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.
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.
Authors: V Paradis; I Bièche; D Dargère; D Cazals-Hatem; I Laurendeau; V Saada; J Belghiti; A Bezeaud; M Vidaud; P Bedossa; D-C Valla Journal: Gut Date: 2005-09-14 Impact factor: 23.059
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