The β-catenin pathway is activated in focal nodular hyperplasia but not in cirrhotic FNH-like nodules

Background/Aims Focal nodular hyperplasias (FNHs) are benign liver lesions considered to be a hyperplastic response to increased blood flow in normal liver. In contrast, FNH-like lesions/nodules occur in cirrhotic liver but share similar histopathological features. We conducted a transcriptome analysis to identify biological pathways deregulated in FNH. Methods Gene expression profiles obtained in FNH and normal livers were compared. Differentially-expressed genes were validated using quantitative-RT-PCR in 70 benign liver tumors including FNH-like lesions. Results Among the deregulated genes in FNHs, 19 displayed physiological restricted distribution in the normal liver. All six perivenous genes were up-regulated in FNH, whereas 13 periportal genes were down-regulated. Almost all these genes are known to be regulated by β-catenin. Glutamine synthetase was markedly overexpressed in anastomosed areas usually centered on visible veins. Moreover, activated hypophosphorylated β-catenin protein accumulated in FNH in the absence of activating mutations. These results suggest the zonated activation of the β-catenin pathway in FNH, whereas the other benign hepatocellular tumors, including FNH-like lesions, demonstrated an entirely different pattern of β-catenin expression. Conclusions In FNH, increased activation of the β-catenin pathway was found restricted to enlarged perivenous areas. FNH-like nodules may have a different pathogenetic origin.