Diagnostic and prognostic TERT promoter mutations in thyroid fine-needle aspiration biopsy.
Diagnostic and prognostic TERT promoter mutations in thyroid fine-needle aspiration biopsy.
复制标题
甲状腺细针运动活检中的诊断和预后启动子突变。
DOI：
10.1530/erc-14-0359
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发表时间：
2014-10
影响因子：
3.9
通讯作者：
Xing M
中科院分区：
文献类型：
--
作者：
Liu R;Xing M
端粒酶逆转录酶（telomerase reverse transcriptase，TERT）基因启动子区的两个突变（chr 5：1，295，228 C>T和chr 5：1，295，250 C>T）最近在甲状腺癌中被发现，并被证明在甲状腺肿瘤的发病机制中起重要作用。甲状腺细针穿刺活检（FNAB）检测这些突变的诊断和预后潜力尚未研究。在此，我们通过直接DNA测序对308例术前从甲状腺结节中获得的FNAB标本进行了两个TERT启动子突变沿着BRAF V600 E突变的检测，这些标本术后经病理学确诊。我们在0.0%（0/179）的良性甲状腺结节和7.0%（9/129）的分化型甲状腺癌甲状腺结节中发现了TERT启动子突变，代表了100%的诊断特异性和7.0%的敏感性，当与BRAF V600 E检测相结合时，后者上升到38.0%（49/129）。几个TERT启动子突变阳性的甲状腺结节在FNAB上的细胞学不确定。近80%的TERT启动子突变阳性甲状腺结节是具有侵袭性临床病理行为的甲状腺癌，如甲状腺外浸润、淋巴结转移、远处转移、疾病复发或患者死亡。因此，阳性的TERT启动子突变检测不仅可以明确诊断甲状腺结节为癌症，而且还可以在术前识别具有侵袭潜力的癌症。这是第一项关于甲状腺FNAB上的TERT启动子突变的研究，证明了这种新型分子检测在甲状腺结节诊断和甲状腺癌术前风险分层中的价值。因此，在FNAB上检测TERT启动子突变将增强和改善目前以分子为基础的方法来管理甲状腺结节和甲状腺癌。
Two promoter mutations, chr5:1,295,228C>T and chr5:1,295,250C>T, in the gene for telomerase reverse transcriptase (TERT) have been recently identified in thyroid cancers and shown to be important in thyroid tumor pathogenesis. The diagnostic and prognostic potentials of testing these mutations on thyroid fine needle aspiration biopsy (FNAB) have not been investigated. Here, we examined the two TERT promoter mutations along with the BRAF V600E mutation by direct DNA sequencing on 308 FNAB specimens preoperatively obtained from thyroid nodules with postoperatively confirmed pathological diagnoses. We found TERT promoter mutations in 0.0% (0/179) of benign thyroid nodules and 7.0% (9/129) of thyroid nodules of differentiated thyroid cancer, representing a 100% diagnostic specificity and 7.0% sensitivity, with the latter rising to 38.0% (49/129) when combined with BRAF V600E testing. Several TERT promoter mutation-positive thyroid nodules were cytologically indeterminate on FNAB. Nearly 80% of the TERT promoter mutation-positive thyroid nodules were thyroid cancers with aggressive clinicopathological behaviors, such as extrathyroidal invasion, lymph node metastases, distant metastases, disease recurrence or patient death. Thus, a positive TERT promoter mutation test not only definitively diagnoses a thyroid nodule as cancer but also preoperatively identifies a cancer with aggressive potential. This is the first study of TERT promoter mutations on thyroid FNAB, demonstrating the value of this novel molecular testing in the diagnosis of thyroid nodule and preoperative risk stratification of thyroid cancer. Thus, testing of TERT promoter mutations on FNAB will enhance and improve the current molecular-based approaches to the management of thyroid nodule and thyroid cancer.