Molecular pathogenesis of focal nodular hyperplasia and hepatocellular adenoma☆

Focal nodular hyperplasia (FNH) and hepatocellular adenomas (HCAs) are benign tumors that occur in otherwise normal liver parenchyma. FNH is considered to be the result of a hyperplastic response to increased blood flow secondary to vascular malformations. Most FNH are polyclonal and to date, the molecular pathway and mechanisms that are altered in FNH have yet to be elucidated. In contrast, HCAs are consistently monoclonal tumors, which have been divided up into three subtypes of tumors depending on the molecular alteration detected in the tumors: HNF1α inactivation, β-catenin activation and/or an acute inflammatory response in the tumor. These molecular features are closely related to clinical and pathological characteristics, and one of the most critical correlations is the higher risk of malignant transformation for β-catenin activated HCA cases. Moreover, various risk factors, such as oral contraception and obesity, are associated with HCA occurrence and may collaborate with constitutional genetic predisposition related to HNF1α or CYP1B1 germline mutations. Altogether, the recent identification of different molecular pathways that contribute to tumor development has significantly increased our knowledge of benign hepatocellular tumorigenesis. These findings may modify our clinical practice, particularly in the diagnosis and follow-up of HCA patients.

Abbreviations: APC, adenomatosis polyposis coli, CTNNB1, gene coding for β-catenin, FAP, familial adenomatous polyposis coli, FNH, focal nodular hyperplasia, HCA, hepatocellular adenoma, HCC, hepatocellular carcinoma, HNF1α, hepatocyte nuclear factor 1 alpha, HUMARA, human androgen receptor, TCF1, transcription factor 1 coding for HNF1α

Keywords: Hepatocellular adenoma, Focal nodular hyperplasia, Chromosome, Gene mutation, Hepatocyte nuclear factor 1, β-Catenin, Inflammation, Benign tumor, Genetic alteration, SAA, CRP, FABP1, Estrogen, Steatosis