Dingani Nkosi, William E Crowe, Brian J Altman, Zoltán N Oltvai, Ellen J Giampoli, Moises J Velez
{"title":"SATB2 is an Emergent Biomarker of Anaplastic Thyroid Carcinoma: A Series with Comprehensive Biomarker and Molecular Studies.","authors":"Dingani Nkosi, William E Crowe, Brian J Altman, Zoltán N Oltvai, Ellen J Giampoli, Moises J Velez","doi":"10.1007/s12022-024-09833-0","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":55167,"journal":{"name":"Endocrine Pathology","volume":null,"pages":null},"PeriodicalIF":11.3000,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine Pathology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12022-024-09833-0","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
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.
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)。
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.