Liver: Adenoma

2006-03-01   Jessica Zucman-Rossi 

1.Inserm U674, Génomique Fonctionnelle des tumeurs solides, 27 rue Juliette Dodu, 75010 Paris, France

Clinics and Pathology


In 90% of the cases, adenomas are sporadic and only rare cases are developed in a familial context: ( Familial liver adenomatosis). Patients with an inherited mutation in one allele of TCF1/HNF1a may develop maturity onset diabetes of the young type 3 (MODY3) and familial liver adenomatosis, when the second allele is inactivated in hepatocytes by somatic mutation or chromosome deletion.


Hepatocellular adenomas are usually related to oral contraceptive use. The other risk factors are : glycogen storage diseases and the androgen therapy. HA are rare tumours: their estimated incidence in France is approximately one case per 100,000 women. Over the past fifteen years, their incidence has seen a sustained decline in industrialised countries; this trend is probably linked to the reduction in ethinylestradiol doses in oral contraceptives.


These tumours result from a benign proliferation of hepatocytes which destroy the normal architecture of the liver. They are usually hyper-vascularised and typical adenoma corresponds to a proliferation of benign hepatocytes, intermingled with numerous thin-walled vessels, without portal tracts.


Surgery is usually proposed for lesion of more than 3 cm


Hepatocellular adenoma may bleed, or rarely, undergo malignant transformation.


The molecular and pathological classification of hepatocellular adenomas permits the identification of strong genotype-phenotype correlations and suggests that adenomas with beta-catenin activation have a higher risk of malignant transformation.



Germline TCF1/HNF1A mutation can predispose to familial liver adenomatosis

Genes Involved and Proteins

Gene name

HNF1A (HNF1 homeobox A)




Alias: HNF1A, hepatocyte nuclear factor 1 alpha, HNF1, LFB1, M57732, MODY3
More than 50 different HNF1a mutations have been identified in HA. These mutations are distributed mainly from exon 1 to 6. Point mutations, small deletions and insertions were identified. Gene deletions are less frequent.

Gene name

CTNNB1 (Catenin, beta-1)




Description: catenin (cadherin-associated protein), beta 1
Activating mutations are amino-acid substitution in exon 3 or in-frame deletion including part or all exon 3.

Protein description

Beta-catenin is an adherens junction protein. Adherens junctions are critical for the establishment and maintenance of epithelial layers, cells adhesion, signal communication, anchorage of the actin cytoskeleton. CTNNB1 has important functions in the E-cadherin-mediated cell-cell adhesion system and also as a dowstream signaling molecule in the Wnt pathway. Cytoplasmic accumulation of b catenin allows it to translocate to the nucleus to form complexes with transcription factors of the T cell factor-lymphoid enhancer factor (Tcf-Lef) family. b-catenin is assumed to transactivate mostly unknown target genes, which may stimulate cell proliferation (acts as an oncogene) or inhibit apoptosis. The b-catenin level in the cell is regulated by its association with the adenomatous polyposis coli ( APC) tumor suppressor protein, axin and GSK-3b. Phosphorylation of b-catenin by the APC-axin-GSK-3b complex leads to its degradation by the ubiquitin-proteasome system.


Pubmed IDLast YearTitleAuthors
145982632003Familial liver adenomatosis associated with hepatocyte nuclear factor 1alpha inactivation.Bacq Y et al
123550882002Bi-allelic inactivation of TCF1 in hepatic adenomas.Bluteau O et al
122978402002P53 gene and Wnt signaling in benign neoplasms: beta-catenin mutations in hepatic adenoma but not in focal nodular hyperplasia.Chen YW et al
106361052000Liver adenomatosis: reappraisal, diagnosis, and surgical management: eight new cases and review of the literature.Chiche L et al
1739961976Liver-cell adenomas associated with use of oral contraceptives.Edmondson HA et al
24129301985Liver adenomatosis. An entity distinct from liver adenoma?Flejou JF et al
2079871978Familial liver-cell adenomas and diabetes mellitus.Foster JH et al
150016502004Hepatocyte nuclear factor-1 alpha gene inactivation: cosegregation between liver adenomatosis and diabetes phenotypes in two maturity-onset diabetes of the young (MODY)3 families.Reznik Y et al
89454701996Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3).Yamagata K et al
164963202006Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC.Zucman-Rossi J et al


Jessica Zucman-Rossi

Liver: Adenoma

Atlas Genet Cytogenet Oncol Haematol. 2006-03-01

Online version: