5hmC Immunohistochemistry: A Predictor of TERT Promoter Mutational Status in Follicular Thyroid Carcinoma?

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2023-08-01 DOI:10.1369/00221554231190437

Martin Hysek, Samuel L Hellgren, Vincenzo Condello, Yiyi Xu, Catharina Larsson, Jan Zedenius, C Christofer Juhlin

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Abstract

Telomerase reverse transcriptase (TERT) gene aberrancies correlate to adverse prognosis in follicular thyroid carcinoma (FTC). As loss of 5-hydroxymethylcytosine (5hmC) has been associated with TERT promoter mutations in papillary thyroid carcinoma, this study sought to analyze the levels of 5hmC in a cohort of follicular thyroid tumors with available TERT data. A total of 29 tumors (26 FTCs, 2 follicular thyroid tumors of uncertain malignant potential, and 1 oncocytic thyroid carcinoma) with known TERT promoter mutational status and TERT gene expression were assessed for 5hmC immunoreactivity using two antibodies (clones RM236 and 4D9.) Slides were analyzed using a semiquantitative scoring system. Of the 10 tumor cases with aberrant TERT, only 1 scored negative with both antibodies (1/10; 10%), whereas the remaining 9 cases (9/10; 90%) exhibited some positivity for at least one antibody. Of the 19 TERT wild-type tumors, no case was scored negative using RM236, and 2 cases (2/19; 11%) using 4D9. The differences between TERT promoter mutated and wild-type groups were non-significant. The sensitivity and specificity for 5hmC immunohistochemistry (IHC) to detect mutated cases were 10% and 100% (RM236) and 20% and 89% (4D9). Therefore, 5hmC IHC is not a sensitive marker for detecting TERT promoter mutations in follicular thyroid tumors.

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5hmC免疫组织化学:滤泡性甲状腺癌TERT启动子突变状态的预测因子?

端粒酶逆转录酶(TERT)基因异常与滤泡性甲状腺癌(FTC)不良预后相关。由于5-羟甲基胞嘧啶(5hmC)的缺失与乳头状甲状腺癌TERT启动子突变有关，本研究试图利用现有TERT数据分析滤泡性甲状腺肿瘤队列中5hmC的水平。使用两种抗体(克隆RM236和4D9)评估了共有29例已知TERT启动子突变状态和TERT基因表达的肿瘤(26例FTCs, 2例恶性潜能不确定的滤泡性甲状腺肿瘤和1例癌细胞性甲状腺癌)的5hmC免疫反应性。用半定量评分系统对载玻片进行分析。在10例TERT异常的肿瘤病例中，只有1例两种抗体均为阴性(1/10;10%)，其余9例(9/10;90%)至少有一种抗体呈阳性。在19例TERT野生型肿瘤中，没有一例使用RM236评分为阴性，2例(2/19;11%)使用4D9。TERT启动子突变组与野生型组之间差异不显著。5hmC免疫组化(IHC)检测突变病例的敏感性和特异性分别为10%和100% (RM236)和20%和89% (4D9)。因此，5hmC IHC不是检测滤泡性甲状腺肿瘤TERT启动子突变的敏感标志物。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.