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Molecular Biology and Genetics

  • Francesco CettaEmail author

Abstract

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].

Keywords

Focal Nodular Hyperplasia Hepatocellular Adenoma Guanosine Diphosphate Focal Nodular Hyperplasia Lesion HNF1A Mutation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  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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