The beta-catenin pathway is activated in focal nodular hyperplasia but not in cirrhotic FNH-like nodules.
OBJECTIVE
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 beta-catenin. Glutamine synthetase was markedly overexpressed in anastomosed areas usually centered on visible veins. Moreover, activated hypophosphorylated beta-catenin protein accumulated in FNH in the absence of activating mutations. These results suggest the zonated activation of the beta-catenin pathway in FNH, whereas the other benign hepatocellular tumors, including FNH-like lesions, demonstrated an entirely different pattern of beta-catenin expression.


CONCLUSIONS
In FNH, increased activation of the beta-catenin pathway was found restricted to enlarged perivenous areas. FNH-like nodules may have a different pathogenetic origin.
Rebouissou
Sandra
S
Inserm, U674, Génomique fonctionnelle des tumeurs solides, 27 rue Juliette Dodu, Paris F-75010, France.
Couchy
Gabrielle
G
Libbrecht
Louis
L
Balabaud
Charles
C
Imbeaud
Sandrine
S
Auffray
Charles
C
Roskams
Tania
T
Bioulac-Sage
Paulette
P
Zucman-Rossi
Jessica
J
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015536:Down-Regulation / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D005260:Female; D020518:Focal Nodular Hyperplasia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D020869:Gene Expression Profiling; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000235:genetics; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism*
C495270:CTNNB1 protein, human; D012333:RNA, Messenger; D051176:beta Catenin