title: Alterations of the mTOR pathway in hepatic angiomyolipoma with emphasis on the epithelioid variant and loss of heterogeneity of TSC1/TSC2.
abstract: OBJECTIVE
  To determine the significance of the epithelioid type and the corresponding molecular alterations in hepatic angiomyolipoma (AML).
  
  
  RESULTS
  We retrieved 24 samples of hepatic AML to delineate the clinicopathological features and the immunohistochemical expression of components in the mTOR pathway, and employed microsatellite markers to analyse allelic imbalances in the TSC1 and TSC2 regions. Myomatous AML was the most common type, and a predominantly epithelioid cell population was observed in 50% of the samples. Two-thirds of all samples contained <20% of fat tissue. Four cases of monotypic epithelioid AML were discovered without prognostic implications. Elevated phospho-p70S6 kinase expression was noted in 19 samples in the absence of phospho-AKT activity. Loss of heterogeneity (LOH) of TSC1/TSC2 was found in 15 samples. As compared wityh syndromic AML samples, sporadic AML samples showed LOH of microsatellite markers to a limited extent. Only four samples had increased β-catenin expression in the context of concurrent high expression of phospho-p70S6 kinase and phospho-S6 (P = 0.018).
  
  
  CONCLUSIONS
  The low fat content and epithelioid cytomorphology in hepatic AML potentially obstruct preoperative and pathological diagnosis. Alteration of the mTOR pathway and LOH of the tuberous sclerosis complex genes is a frequent pathogenesis in hepatic AMLs.
authors.affiliation: Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan.
authors.forename: Shih-Chiang
authors.initials: SC
authors.lastname: Huang
authors.forename: Huei-Chieh
authors.initials: HC
authors.lastname: Chuang
authors.forename: Tai-Di
authors.initials: TD
authors.lastname: Chen
authors.forename: Chen-Lin
authors.initials: CL
authors.lastname: Chi
authors.forename: Kwai-Fong
authors.initials: KF
authors.lastname: Ng
authors.forename: Ta-Sen
authors.initials: TS
authors.lastname: Yeh
authors.forename: Tse-Ching
authors.initials: TC
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D018207:Angiomyolipoma / Q000378:metabolism* / Q000473:pathology; D015622:Epithelioid Cells / Q000473:pathology*; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D046888:Tissue Array Analysis; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: angiomyolipoma; epithelioid; liver; mTOR; tuberous sclerosis