Identification of Recurrent TERT Promoter Mutations in Intrathyroid Thymic Carcinomas
Identification of Recurrent TERT Promoter Mutations in Intrathyroid Thymic Carcinomas
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DOI：
10.1007/s12022-020-09635-0
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发表时间：
2020-06-27
影响因子：
4.4
通讯作者：
Kondo, Tetsuo
中科院分区：
文献类型：
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作者：
Tahara, Ippei;Oishi, Naoki;Kondo, Tetsuo
甲状腺内胸腺癌(ITTC)是一种罕见的恶性肿瘤，被认为是异位于甲状腺的在位胸腺癌。组织病理学上，ITTC类似于胸腺鳞状细胞癌，其TC标志物如CD5和c-kit呈阳性。尽管有这些相似的组织学发现，ITTC在临床上没有TC那么侵袭性。在这项研究中，我们比较了ITTC和TCS的临床、组织学和遗传学特征。我们收集了9个ITTC和8个TC及其临床病理特征。采用免疫组织化学方法检测CD5、p63、CD117/c-kit、Ki-67、P53、TTF-1、甲状腺球蛋白、PAX8、EGFR、PD-L1/CD274+EBER的表达。我们用Sanger测序进一步研究了KIT、EGFR、BRAF和TERT启动子的突变情况。在我们的研究中，ITTC影响的患者比TCS年轻得多。平均随访86个月，所有ITTC患者均存活，而两名TC患者已死亡。免疫组织化学显示，除EGFR和P53外，ITTCs和TCS具有相似的免疫表型。基因分析未发现任何ITTC或TC中存在KITR或BRAF突变。EGFR突变在11%(1/9)的ITTCs和25%(2/8)的TCS中呈阳性。值得注意的是，在22%(2/9)的ITTC中发现了TERT启动子C228T突变，但在所有ITTC中均未发现突变。TERT突变和TERT野生型ITTCs在年龄、肿瘤大小或性别上没有显著差异。总的来说，ITTC和TC具有相似的组织病理学和免疫表型特征，但临床结果不同。复发TERT启动子突变可能是ITTCs中与肿瘤进展有关的一个关键事件，值得进一步研究。
Intrathyroid thymic carcinoma (ITTC) is a rare malignant neoplasm considered to be a eutopic thymic carcinoma (TC) arising ectopically in the thyroid. Histopathologically, ITTC resembles squamous cell carcinoma of the thymus with positive TC markers such as CD5 and c-KIT. Despite these similar histological findings, ITTC is clinically less aggressive than TC. In this study, we compared clinical, histological, and genetic characteristics of ITTCs and TCs. We collected 9 ITTCs and 8 TCs with their clinicopathological profiles. Immunohistochemistry for CD5, p63, CD117/c-KIT, Ki-67, p53, TTF-1, thyroglobulin, PAX8, EGFR, and PD-L1/CD274 plus in situ hybridization for EBER was performed. We further investigated mutation status ofKIT,EGFR,BRAF, andTERTpromoter using Sanger sequencing. In our study, ITTCs affected significantly younger patients than TCs. After a mean follow-up of 86 months, all patients with ITTC were alive, while two patients with TC had died. Immunohistochemistry showed ITTCs and TCs had a similar immunophenotype except for EGFR and p53. Genetic analysis did not identifyKITorBRAFmutations in any ITTCs or TCs.EGFRmutations were positive in 11% (1/9) of ITTCs and 25% (2/8) of TCs. Notably,TERTpromoter C228T mutation was identified in 22% (2/9) of ITTCs but none of the TCs. There were no significant differences in age, tumor size, or sex betweenTERT-mutated andTERT-wild-type ITTCs. Collectively, ITTC and TC have similar histopathologic and immunophenotypic features but different clinical outcomes. RecurrentTERTpromoter mutation may be a key event related to cancer progression in ITTCs and warrants further investigation.