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  • Title: A quantitative gene expression study suggests a role for angiopoietins in focal nodular hyperplasia.
    Author: Paradis V, Bièche I, Dargère D, Laurendeau I, Nectoux J, Degott C, Belghiti J, Vidaud M, Bedossa P.
    Journal: Gastroenterology; 2003 Mar; 124(3):651-9. PubMed ID: 12612904.
    Abstract:
    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.
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