SATB2 is an Emergent Biomarker of Anaplastic Thyroid Carcinoma: A Series with Comprehensive Biomarker and Molecular Studies.

IF 11.3 2区医学 Q1 ENDOCRINOLOGY & METABOLISM Endocrine Pathology Pub Date : 2024-11-05 DOI:10.1007/s12022-024-09833-0

Dingani Nkosi, William E Crowe, Brian J Altman, Zoltán N Oltvai, Ellen J Giampoli, Moises J Velez

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Abstract

Anaplastic thyroid carcinoma (ATC) is a rare and aggressive thyroid malignancy typically comprised of undifferentiated tumor cells with various histologic morphologies, which makes the diagnosis challenging. These tumors commonly show loss of thyroglobulin and TTF1 with preservation of cytokeratin (67%) and Paired Box Gene 8 (PAX8) (55%) expression. Identification of a sensitive immunohistochemical stain to aid in the diagnosis of ATC would be beneficial. Immunohistochemistry (IHC) against special AT-rich sequence-binding protein 2 (SATB2) protein is a sensitive and specific marker expressed in colorectal adenocarcinoma and bone or soft tissue tumors with osteoblastic differentiation. However, SATB2 is also expressed in other sarcomatous/undifferentiated neoplasms lacking osteoblastic differentiation. Using quantitative reverse transcription PCR (RT-qPCR) we showed that there is variable expression of SATB2 mRNA expression in ATCs. To evaluate the role of SATB2 protein expression in ATC, we performed PAX8, SATB2, pancytokeratin (AE1/AE3 & CAM5.2), claudin-4 and TTF1 immunostaining on 23 cases. ATCs showed retained expression of PAX8 in 65% (15/23); SATB2 was detected in 74% (17/23); pancytokeratin was expressed in 65% (15/23); claudin-4 was expressed in 35% (8/23) and TTF1 showed expression in 13% (3/23) of cases. Furthermore, 83% (5/6) of ATCs which lacked SATB2 expression, retained PAX8 expression, while 88% (7/8) of the tumors without PAX8 expression were positive for SATB2. Differentiated follicular cell-derived thyroid cancers (n = 30), differentiated high grade thyroid carcinoma (n = 3), and poorly differentiated thyroid carcinoma (n = 8) were negative for SATB2 immunoreactivity. Next-generation selected cases detected the commonly identified oncogenic variants including those in BRAF, RAS, TP53, and TERT promoter. Overall, we hereby demonstrate that SATB2 IHC may be used to support the diagnosis of ATC.

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SATB2 是甲状腺无节细胞癌的新兴生物标志物：综合生物标志物和分子研究系列报告》（SATB2 is an Emergent Biomarker of Anaplastic Thyroid Carcinoma: A Series with Comprehensive Biomarker and Molecular Studies）。

甲状腺无分化癌（ATC）是一种罕见的侵袭性甲状腺恶性肿瘤，通常由具有不同组织学形态的未分化肿瘤细胞组成，因此诊断具有挑战性。这些肿瘤通常表现为甲状腺球蛋白和TTF1的缺失，而细胞角蛋白（67%）和配对盒基因8（PAX8）（55%）的表达却得以保留。确定一种敏感的免疫组化染色方法来帮助诊断 ATC 将是有益的。针对特殊富AT序列结合蛋白2（SATB2）蛋白的免疫组化（IHC）是在结直肠腺癌和具有成骨细胞分化的骨或软组织肿瘤中表达的一种敏感而特异的标记物。然而，SATB2 在其他缺乏成骨细胞分化的肉瘤/未分化肿瘤中也有表达。通过使用定量反转录 PCR（RT-qPCR），我们发现 SATB2 mRNA 在 ATC 中的表达存在差异。为了评估 SATB2 蛋白表达在 ATC 中的作用，我们对 23 例病例进行了 PAX8、SATB2、泛型角蛋白（AE1/AE3 和 CAM5.2）、claudin-4 和 TTF1 免疫染色。结果显示，65%（15/23）的 ATC 保留表达 PAX8；74%（17/23）的 ATC 检测到 SATB2；65%（15/23）的 ATC 表达 pancytokeratin；35%（8/23）的 ATC 表达 claudin-4；13%（3/23）的 ATC 表达 TTF1。此外，83%（5/6）缺乏 SATB2 表达的 ATC 保留了 PAX8 表达，而 88%（7/8）没有 PAX8 表达的肿瘤 SATB2 呈阳性。分化型滤泡细胞源性甲状腺癌（30例）、分化型高级别甲状腺癌（3例）和分化不良型甲状腺癌（8例）的SATB2免疫反应均为阴性。经下一代筛选的病例检测出了常见的致癌变体，包括BRAF、RAS、TP53和TERT启动子中的变体。总之，我们在此证明 SATB2 IHC 可用于支持 ATC 的诊断。

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来源期刊

Endocrine Pathology 医学-病理学

CiteScore

12.30

自引率

20.50%

发文量

审稿时长

>12 weeks

期刊介绍： Endocrine Pathology publishes original articles on clinical and basic aspects of endocrine disorders. Work with animals or in vitro techniques is acceptable if it is relevant to human normal or abnormal endocrinology. Manuscripts will be considered for publication in the form of original articles, case reports, clinical case presentations, reviews, and descriptions of techniques. Submission of a paper implies that it reports unpublished work, except in abstract form, and is not being submitted simultaneously to another publication. Accepted manuscripts become the sole property of Endocrine Pathology and may not be published elsewhere without written consent from the publisher. All articles are subject to review by experienced referees. The Editors and Editorial Board judge manuscripts suitable for publication, and decisions by the Editors are final.