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Alterations of the m TOR pathway in hepatic angiomyolipoma with emphasis on the epithelioid variant and loss of heterogeneity of TSC 1 / TSC2
Author(s) -
Huang ShihChiang,
Chuang HueiChieh,
Chen TaiDi,
Chi ChenLin,
Ng KwaiFong,
Yeh TaSen,
Chen TseChing
Publication year - 2015
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12551
Subject(s) - angiomyolipoma , tuberous sclerosis , tsc1 , tsc2 , biology , pathology , context (archaeology) , immunohistochemistry , population , cancer research , pi3k/akt/mtor pathway , medicine , endocrinology , genetics , signal transduction , paleontology , environmental health , kidney
Aims To determine the significance of the epithelioid type and the corresponding molecular alterations in hepatic angiomyolipoma ( AML ). Methods and results We retrieved 24 samples of hepatic AML to delineate the clinicopathological features and the immunohistochemical expression of components in the m TOR pathway, and employed microsatellite markers to analyse allelic imbalances in the TSC 1 and TSC 2 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 TSC 1 / TSC 2 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 m TOR pathway and LOH of the tuberous sclerosis complex genes is a frequent pathogenesis in hepatic AML s.