乳腺乳头状肿瘤 IDH2 R172 热点突变的免疫组织化学分析：在反极性高细胞癌诊断中的应用。,Modern Pathology

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乳腺乳头状肿瘤 IDH2 R172 热点突变的免疫组织化学分析：在反极性高细胞癌诊断中的应用。
Modern Pathology ( IF 7.1 ) Pub Date : 2020-01-02 , DOI: 10.1038/s41379-019-0442-2
Fresia Pareja ₁ , Edaise M da Silva ₁ , Denise Frosina ₁ , Felipe C Geyer ₁ , John R Lozada ₁ , Thais Basili ₁ , Arnaud Da Cruz Paula ₂ , Elaine Zhong ₃ , Fatemeh Derakhshan ₄ , Timothy D'Alfonso ₁ , Hannah Y Wen ₁ , Dilip D Giri ₁ , Malcolm M Hayes ₄ , Gregor Krings ₅ , Rohit Bhargava ₆ , Juan P Palazzo ₇ , Emad A Rakha ₈ , Syed A Hoda ₃ , Melinda E Sanders ₉ , Laura C Collins ₁₀ , Stuart J Schnitt ₁₁ , Yunn-Yi Chen ₅ , Britta Weigelt ₁ , Achim A Jungbluth ₁ , Jorge S Reis-Filho ₁ , Edi Brogi ₁

Affiliation

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY, USA.
Department of Pathology, British Columbia Cancer Agency, Vancouver, BC, Canada.
Department of Pathology at Mission Bay, University of California San Francisco, San Francisco, CA, USA.
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Pathology, Baptist Health South Florida, Miami, FL, USA.
Division of Cancer and Stem Cells, School of Medicine, The University of Nottingham, Nottingham City Hospital, UK.
Department of Pathology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School; Dana-Farber Cancer Institute, Boston, MA, USA.

具有反极性的高细胞癌是一种罕见的乳腺癌亚型，具有实体和乳头状生长以及核特征，让人联想到甲状腺乳头状癌的高细胞变体。这些肿瘤具有复发性 IDH2 R172 热点突变或 TET2 突变，与 PI3K 通路基因突变同时发生。鉴于其罕见性和鉴别诊断的范围，具有反极性的高细胞癌的诊断具有挑战性。我们试图确定 IDH2 R172 免疫组织化学检测该实体中 IDH2 R172 热点突变的敏感性和特异性。我们评估了 14 例反极性高细胞癌（10 例切除标本和 5 例核心针活检标本）、13 例导管内乳头状瘤、16 例实性乳头状癌、通过对 IDH2 R172 热点基因座和 PIK3CA 外显子 9 和 20 进行 Sanger 测序，以及使用针对 IDH2 R172S 突变的单克隆抗体 (11C8B1) 进行免疫组织化学分析，对 5 例有包膜的乳头状癌进行了测序。所研究的 14 例反极性高细胞癌携带 IDH2 R172 热点突变，在 50% 的病例中与 PIK3CA 热点突变同时发生。分析的其他乳头状肿瘤均未显示 IDH2 R172 突变，但在 54% 的导管内乳头状瘤、6% 的实性乳头状癌和 20% 的包膜乳头状癌中检测到 PIK3CA 热点突变。使用抗 IDH2 R172S 抗体 (11C8B1) 进行的免疫组织化学分析在 93% (14/15) 的高细胞癌中检测到 IDH2 R172 突变蛋白，具有反极性样本，包括切除样本 (n = 9/10) 和核心针活检样本 (n = 5) )，而其余乳头状肿瘤 (n = 34) 为阴性。我们的研究结果表明，IDH2 R172 的免疫组织化学分析对于检测 IDH2 R172 热点突变具有高度敏感性和特异性，并且可能适合作为评估具有反极性的高细胞癌切除和核心针活检材料的诊断工具。

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Immunohistochemical analysis of IDH2 R172 hotspot mutations in breast papillary neoplasms: applications in the diagnosis of tall cell carcinoma with reverse polarity.

Tall cell carcinoma with reverse polarity is a rare subtype of breast carcinoma with solid and papillary growth and nuclear features reminiscent of those of the tall cell variant of papillary thyroid carcinoma. These tumors harbor recurrent IDH2 R172 hotspot mutations or TET2 mutations, co-occurring with mutations in PI3K pathway genes. Diagnosis of tall cell carcinomas with reverse polarity is challenging in view of their rarity and the range of differential diagnosis. We sought to determine the sensitivity and specificity of IDH2 R172 immunohistochemistry for the detection of IDH2 R172 hotspot mutations in this entity. We evaluated 14 tall cell carcinomas with reverse polarity (ten excision and five core needle biopsy specimens), 13 intraductal papillomas, 16 solid papillary carcinomas, and 5 encapsulated papillary carcinomas by Sanger sequencing of the IDH2 R172 hotspot locus and of exons 9 and 20 of PIK3CA, and by immunohistochemistry using monoclonal antibodies (11C8B1) to the IDH2 R172S mutation. The 14 tall cell carcinomas with reverse polarity studied harbored IDH2 R172 hotspot mutations, which co-occurred with PIK3CA hotspot mutations in 50% of cases. None of the other papillary neoplasms analyzed displayed IDH2 R172 mutations, however PIK3CA hotspot mutations were detected in 54% of intraductal papillomas, 6% of solid papillary carcinomas, and 20% of encapsulated papillary carcinomas tested. Immunohistochemical analysis with anti-IDH2 R172S antibodies (11C8B1) detected IDH2 R172 mutated protein in 93% (14/15) of tall cell carcinomas with reverse polarity samples including excision (n = 9/10) and core needle biopsy specimens (n = 5), whereas the remaining papillary neoplasms (n = 34) were negative. Our findings demonstrate that immunohistochemical analysis of IDH2 R172 is highly sensitive and specific for the detection of IDH2 R172 hotspot mutations, and likely suitable as a diagnostic tool in the evaluation of excision and core needle biopsy material of tall cell carcinomas with reverse polarity.

更新日期：2020-01-04

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