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Genotype-phenotype correlation in hepatocellular adenoma: new classification and relationship with HCC
- Source :
- Hepatology, Hepatology, Wiley-Blackwell, 2006, 43 (3), pp.515-24. ⟨10.1002/hep.21068⟩, Hepatology, 2006, 43 (3), pp.515-24. ⟨10.1002/hep.21068⟩, Hepatology, Wiley-Blackwell, 2006, 43 (3), pp.515-24. 〈10.1002/hep.21068〉
- Publication Year :
- 2006
- Publisher :
- HAL CCSD, 2006.
-
Abstract
- Hepatocellular adenomas are benign tumors that can be difficult to diagnose. To refine their classification, we performed a comprehensive analysis of their genetic, pathological, and clinical features. A multicentric series of 96 liver tumors with a firm or possible diagnosis of hepatocellular adenoma was reviewed by liver pathologists. In all cases, the genes coding for hepatocyte nuclear factor 1alpha (HNF1alpha) and beta-catenin were sequenced. No tumors were mutated in both HNF1alpha and beta-catenin enabling tumors to be classified into 3 groups, according to genotype. Tumors with HNF1alpha mutations formed the most important group of adenomas (44 cases). They were phenotypically characterized by marked steatosis (P < 10(-4)), lack of cytological abnormalities (P < 10(-6)), and no inflammatory infiltrates (P < 10(-4)). In contrast, the group of tumors defined by beta-catenin activation included 13 lesions with frequent cytological abnormalities and pseudo-glandular formation (P < 10(-5)). The third group of tumors without mutation was divided into two subgroups based on the presence of inflammatory infiltrates. The subgroup of tumors consisting of 17 inflammatory lesions, resembled telangiectatic focal nodular hyperplasias, with frequent cytological abnormalities (P = 10(-3)), ductular reaction (P < 10(-2)), and dystrophic vessels (P = .02). In this classification, hepatocellular carcinoma associated with adenoma or borderline lesions between carcinoma and adenoma is found in 46% of the beta-catenin-mutated tumors whereas they are never observed in inflammatory lesions and are rarely found in HNF1alpha mutated tumors (P = .004). In conclusion, 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.
- Subjects :
- Male
Pathology
MESH : Liver Neoplasms
MESH : Retrospective Studies
MESH: beta Catenin
MESH : Aged
MESH : Genotype
Malignant transformation
MESH: Genotype
MESH: Adenoma, Liver Cell
0302 clinical medicine
MESH: Liver Neoplasms
MESH : Female
Hepatocyte Nuclear Factor 1-alpha
MESH: Carcinoma, Hepatocellular
beta Catenin
MESH: Aged
MESH: Middle Aged
Liver Neoplasms
MESH : Adult
Middle Aged
3. Good health
MESH : Phenotype
Phenotype
030220 oncology & carcinogenesis
Hepatocellular carcinoma
MESH : Hepatocyte Nuclear Factor 1-alpha
[ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Female
030211 gastroenterology & hepatology
MESH : Mutation
MESH : Carcinoma, Hepatocellular
Adult
medicine.medical_specialty
Carcinoma, Hepatocellular
MESH: Mutation
Adolescent
Genotype
Adenoma
MESH : Male
Biology
MESH: Phenotype
Adenoma, Liver Cell
03 medical and health sciences
MESH : Adenoma, Liver Cell
MESH : Adolescent
medicine
Carcinoma
Humans
MESH : Middle Aged
MESH: Hepatocyte Nuclear Factor 1-alpha
Pathological
Aged
Retrospective Studies
MESH: Adolescent
MESH: Humans
Hepatology
MESH : Humans
MESH: Retrospective Studies
MESH: Adult
[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
Hepatocellular adenoma
MESH : beta Catenin
medicine.disease
[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology
digestive system diseases
MESH: Male
Mutation
Inflammatory Hepatocellular Adenoma
Steatosis
MESH: Female
Subjects
Details
- Language :
- English
- ISSN :
- 02709139 and 15273350
- Database :
- OpenAIRE
- Journal :
- Hepatology, Hepatology, Wiley-Blackwell, 2006, 43 (3), pp.515-24. ⟨10.1002/hep.21068⟩, Hepatology, 2006, 43 (3), pp.515-24. ⟨10.1002/hep.21068⟩, Hepatology, Wiley-Blackwell, 2006, 43 (3), pp.515-24. 〈10.1002/hep.21068〉
- Accession number :
- edsair.doi.dedup.....04ff6e55304ce79a4f76868ce887b5e8