Hepatocellular adenoma classification: a comparative evaluation of immunohistochemistry and targeted mutational analysis
Hepatocellular adenoma classification: a comparative evaluation of immunohistochemistry and targeted mutational analysis
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DOI：
10.1186/s13000-016-0475-5
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发表时间：
2016-03-09
影响因子：
2.6
通讯作者：
Salomao, Marcela
中科院分区：
文献类型：
--
作者：
Margolskee, Elizabeth;Bao, Fei;Salomao, Marcela
背景：肝细胞腺瘤分为四种亚型：肝细胞核因子-1α突变型(H-HCA)、谷氨酰胺合成酶上调的β-连环蛋白突变型(b-HCA)、血清淀粉样蛋白A高表达的炎症型(IHCA)和未分型。亚型可能是有用的，因为b-HCA似乎有更高的恶变风险。方法：应用血清淀粉样蛋白A(SAA)、肝脏脂肪酸结合蛋白(LFABP)、谷氨酰胺合成酶(GS)和β-连环素IHC对26例肝细胞癌进行亚型分析和组织学非典型性评估。结果：根据IHC，4例(15.4%)为b-HCA，11(42.3%)为IHCA，9(34.6%)为H-HCA，2(7.7%)为不可分型。8例(30.8%)表现为非典型性，包括3例b-HCA、4例IHCA和1例H-HCA。靶向测序证实了所有H-HCA中的HNF1A突变，证实了LFABP IHC在识别这些病变方面的可靠性。在4例GS/β-catenin阳性的病例中，有1例(25%)检测到CTNNB1突变，提示GS染色阳性并不总是与CTNNB1突变相关。突变分析提高了β-连环蛋白突变的HCA的诊断准确性，是评估HCA恶变风险的重要工具。
Background: Four subtypes of hepatocellular adenomas (HCA) are recognized: hepatocyte-nuclear-factor-1 alpha mutated (H-HCA), beta-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 beta-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/beta-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 beta-catenin-mutated HCA and is an important tool to assess risk of malignancy in HCA.