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Hepatocellular adenoma classification: a comparative evaluation of
immunohistochemistry and targeted mutational analysis
#MMPMID26961851
Margolskee E
; Bao F
; de Gonzalez AK
; Moreira RK
; Lagana S
; Sireci AN
; Sepulveda AR
; Remotti H
; Lefkowitch JH
; Salomao M
Diagn Pathol
2016[Mar]; 11
(?): 27
PMID26961851
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BACKGROUND: Four subtypes of hepatocellular adenomas (HCA) are recognized:
hepatocyte-nuclear-factor-1? mutated (H-HCA), ?-catenin-mutated type with
upregulation of glutamine synthetase (b-HCA), inflammatory type (IHCA) with
serum-amyloid-A overexpression, and unclassified type. Subtyping may be useful
since b-HCA appear to have higher risk of malignant transformation. We sought to
apply subtype analysis and assess histological atypia, correlating these with
next-generation sequencing analysis. METHODS: Twenty-six HCA were stained with
serum amyloid A (SAA), liver fatty acid-binding protein (LFABP), glutamine
synthetase (GS), and ?-catenin IHC, followed by analysis with a targeted
multiplex sequencing panel. RESULTS: By IHC, 4 HCA (15.4 %) were classified as
b-HCA, 11 (42.3 %) as IHCA, 9 (34.6 %) as H-HCA, and two (7.7 %) unclassifiable.
Eight HCA (30.8 %) showed atypia (3 b-HCA, 4 IHCA and 1 H-HCA). Targeted
sequencing confirmed HNF1A mutations in all H-HCA, confirming reliability of
LFABP IHC in identifying these lesions. CTNNB1 mutations were detected in 1 of 4
(25 %) of GS/?-catenin-positive cases, suggesting that positive GS stain does not
always correlate with CTNNB1 mutations. CONCLUSIONS: Immunohistochemistry does
not consistently identify b-HCA. Mutational analysis improves the diagnostic
accuracy of ?-catenin-mutated HCA and is an important tool to assess risk of
malignancy in HCA.
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