Molecular Biology and Genetics

  • Francesco CettaEmail author


Hepatocellular benign tumors are characterized by benign proliferation of hepatocytes with a mass-forming presentation and mainly consist of hepatocellular adenoma (HA) and focal nodular hyperplasia (FNH) [1, 2]. HA and FNH share common features. First, a large female preponderance has been found in both diseases, with a female/male ratio = 8:1 for FNH and 9:1 for HA. In addition, FNH and HA derive from the proliferation of mature hepatocytes and arise on an otherwise normal liver. Therefore, they represent a model to study liver tumorigenesis outside the classic background of cirrhosis [2].


Focal Nodular Hyperplasia Hepatocellular Adenoma Guanosine Diphosphate Focal Nodular Hyperplasia Lesion HNF1A Mutation 
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  1. 1.
    Shaked O, Siegelman ES, Olthoff K, Reddy KR (2011) Biologic and clinical features of benign solid and cystic lesions of the liver. Clin Gastroenterol Hepatol 9:547–562CrossRefPubMedGoogle Scholar
  2. 2.
    Nault J-C, Bioulac-Sage P, Zucmann-Rossi J (2013) Hepatocellular benign tumors- from molecular classification to personalized clinical care. Gastroenterology 144:888–902CrossRefPubMedGoogle Scholar
  3. 3.
    Bioulac-Sage P, Cubel G, Balabaud C et al (2011) Revisiting the pathology of resected benign hepatocellular nodules using new immunohistochemical markers. Semin Liver Dis 31:91–103CrossRefPubMedGoogle Scholar
  4. 4.
    Bioulac-Sage P, Rebouissou S, Sa Cunha A et al (2005) Clinical, morphologic, and molecular features defining so-called telangiectatic focal nodular hyperplasias of the liver. Gastroenterology 128:1211–1218CrossRefPubMedGoogle Scholar
  5. 5.
    Bioulac-Sage P, Blanc JF, Rebouissou S et al (2007) Genotype phenotype classification of hepatocellular adenoma. World J Gastroenterol 13:2649–2654CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Zucman-Rossi J, Jeannot E, Nhieu JTV et al (2006) Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC. Hepatology 43:515–524CrossRefPubMedGoogle Scholar
  7. 7.
    Bioulac-Sage P, Laumonier H, Couchy G et al (2009) Hepatocellular adenoma management and phenotypic classification: the Bordeaux experience. Hepatology 50:481–489CrossRefPubMedGoogle Scholar
  8. 8.
    Bioulac-Sage P, Rebouissou S, Thomas C et al (2007) Hepatocellular adenoma subtype classification using molecular markers and immunohistochemistry. Hepatology 46:740–748CrossRefPubMedGoogle Scholar
  9. 9.
    Benhamouche S, Decaens T, Godard C et al (2006) Apc tumor suppressor gene is the “zonation-keeper” of mouse liver. Dev Cell 10:759–770CrossRefPubMedGoogle Scholar
  10. 10.
    Reznik Y, Dao T, Coutant R et al (2004) Hepatocyte nuclear factor- 1 alpha gene inactivation: co-segregation between liver adenomatosis and diabetes phenotypes in two maturity-onset diabetes of the young (MODY) 3 families. J Clin Endocrinol Metab 89:1476–1480CrossRefPubMedGoogle Scholar
  11. 11.
    Bunchorntavakul C, Bahirwani R, Drazek D et al (2011) Clinical features and natural history of hepatocellular adenomas: the impact of obesity. Aliment Pharmacol Ther 34:664–674CrossRefPubMedGoogle Scholar
  12. 12.
    Bioulac-Sage P, Taouji S, Possenti L et al (2012) Hepatocellular adenomas subtypes. The impact of overweight and obesity. Liver Int 32:1217–1221CrossRefPubMedGoogle Scholar
  13. 13.
    Watkins J, Balabaud C, Bioulac-Sage P et al (2009) Hepatocellular adenoma in advanced-stage fatty liver disease. Eur J Gastroenterol Hepatol 21:932–936CrossRefPubMedGoogle Scholar
  14. 14.
    Lerut JP, Ciccarelli O, Sempoux C et al (2003) Glycogenosis storage type I diseases and evolutive adenomatosis: an indication for liver transplantation. Transpl Int 16:879–884CrossRefPubMedGoogle Scholar
  15. 15.
    Calderaro J, Labrune P, Morcrette G et al (2013) Molecular characterization of hepatocellular adenomas developed in patients with glycogen storage disease type I. J Hepatol 58:350–357CrossRefPubMedGoogle Scholar
  16. 16.
    Mutel E, Abdul-Wahed A, Ramamonjisoa N et al (2011) Targeted deletion of liver glucose-6 phosphatase mimics glycogen storage disease type 1a including development of multiple adenomas. J Hepatol 54:529–537CrossRefPubMedGoogle Scholar
  17. 17.
    Jeannot E, Poussin K, Chiche L et al (2007) Association of CYP1B1 germ line mutations with hepatocyte nuclear factor 1 alpha mutated hepatocellular adenoma. Cancer Res 67:2611–2616CrossRefPubMedGoogle Scholar
  18. 18.
    Vilgrain V, Fléjou JF, Arrivé L et al (1992) Focal nodular hyperplasia of the liver: MR imaging and pathologic correlation in 37 patients. Radiology 184:699–703CrossRefPubMedGoogle Scholar
  19. 19.
    Paradis V, Laurent A, Flejou JF et al (1997) Evidence for the polyclonal nature of focal nodular hyperplasia of the liver by the study of X-chromosome inactivation. Hepatology 26:891–895CrossRefPubMedGoogle Scholar
  20. 20.
    Paradis V, Bièche I, Dargère D et al (2003) A quantitative gene expression study suggests a role for angiopoietins in focal nodular hyperplasia. Gastroenterology 124:651–659CrossRefPubMedGoogle Scholar
  21. 21.
    Rebouissou S, Bioulac-Sage P, Zucman-Rossi J (2008) Molecular pathogenesis of focal nodular hyperplasia and hepatocellular adenoma. J Hepatol 48:163–170CrossRefPubMedGoogle Scholar
  22. 22.
    Bioulac-Sage P, Laumonier H, Rullier A et al (2009) Over-expression of glutamine synthetase in focal nodular hyperplasia: a novel easy diagnostic tool in surgical pathology. Liver Int 29:459–465CrossRefPubMedGoogle Scholar
  23. 23.
    Chen Y-W, Jeng Y-M, Yeh S-H, Chen P-J (2002) P53 gene and Wnt signaling in benign neoplasms: beta-catenin mutations in hepatic adenoma but not in focal nodular hyperplasia. Hepatology 36:927–935CrossRefPubMedGoogle Scholar
  24. 24.
    Rebouissou S, Couchy G, Libbrecht L et al (2008) The beta-catenin pathway is activated in focal nodular hyperplasia but not in cirrhotic FNH-like nodules. J Hepatol 49:61–71CrossRefPubMedGoogle Scholar
  25. 25.
    Gaffey MJ, Iezzoni JC, Weiss LM (1996) Clonal analysis of focal nodular hyperplasia of the liver. Am J Pathol 148:1089–1096PubMedCentralPubMedGoogle Scholar
  26. 26.
    Cai Y-R, Gong L, Teng X-Y et al (2009) Clonality and allelotype analyses of focal nodular hyperplasia compared with hepatocellular adenoma and carcinoma. World J Gastroenterol 15:4695–4708CrossRefPubMedCentralPubMedGoogle Scholar
  27. 27.
    Turowski C, Feist H, Alzen G et al (2009) Conversion of a neonatal hepatic hemangioma to focal nodular hyperplasia. Pathol Int 59:251–254CrossRefPubMedGoogle Scholar
  28. 28.
    Scoazec JY, Flejou JF, D’Errico A et al (1995) Focal nodular hyperplasia of the liver: composition of the extracellular matrix and expression of cell-cell and cell-matrix adhesion molecules. Hum Pathol 26:1114–1125CrossRefPubMedGoogle Scholar
  29. 29.
    Renieri A, Mencarelli MA, Cetta F et al (2014) Oligogenic germline mutations identified in early non-smokers lung adenocarcinoma patients. Lung Cancer 85:168–174CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG Switzerland 2015

Authors and Affiliations

  1. 1.IRCCS MultiMedicaMilanItaly

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