Tan Li-Cheng, Liu Wan-Lin, Zhu Xiao-Li, Yu Peng-Cheng, Shi Xiao, Han Pei-Zhen, Zhang Ling, Lin Liang-Yu, Semenov Arseny, Wang Yu, Ji Qing-Hai, Ji Dong-Mei, Wang Yu-Long, Qu Ning
Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Front Oncol. 2021 Jul 12;11:677892. doi: 10.3389/fonc.2021.677892. eCollection 2021.
Though fine-needle aspiration (FNA) improved the diagnostic methods of thyroid nodules, there are still parts of nodules that cannot be determined according to cytology. In the Bethesda system for reporting thyroid cytopathology, there are two uncertain cytology results. Thanks to the development of next-generation sequencing technology, it is possible to gain the genetic background of pathological tissue efficiently. Therefore, a combination of the cytology and genetic background may enhance the accuracy of diagnosis in thyroid nodules.
DNA from 73 FNA samples of thyroid nodules belonging to different cytology types was extracted and exome sequencing was performed by the ThyroLead panel. Test for BRAF mutation was also performed by ARMS-qPCR. Information including age, sex, preoperative cytology, mutation status tested by ARMS-qPCR, and surgical pathology was collected in electronic medical record system.
A total of 71 single nucleotide variants, three fusion gene, and two microsatellite instability-high status were detected in 73 FNA samples. BRAF V600E mutation is the most common mutation in these malignant thyroid nodules. After combining the cytology and genetic background detected by next-generation sequencing, the diagnosis sensitivity was increased from 0.582 (95% CI: 0.441-0.711) to 0.855 (95% CI: 0.728-0.930) ( < 0.001) in our group, while the specificity, 1,000 (95% CI: 0.732-1.000) compared to 0.857 (95% CI: 0.562-0.975) ( = 0.25), did not get affected.
Next-generation sequencing in thyroid nodules can enhance the preoperative diagnosis sensitivity by fine-needle aspiration alone. It can also provide genetic background for direction of medication. It is possible for clinicians to combine cytology with genetic alterations for a more precise diagnosis strategy of thyroid nodules.
尽管细针穿刺活检（FNA）改善了甲状腺结节的诊断方法，但仍有部分结节无法通过细胞学检查来确定。在甲状腺细胞病理学报告的贝塞斯达系统中，存在两种不确定的细胞学结果。得益于新一代测序技术的发展，高效获取病理组织的基因背景成为可能。因此，细胞学与基因背景相结合可能会提高甲状腺结节诊断的准确性。
提取73份属于不同细胞学类型的甲状腺结节FNA样本的DNA，并通过ThyroLead检测板进行外显子组测序。还通过ARMS-qPCR检测BRAF突变。在电子病历系统中收集年龄、性别、术前细胞学检查、ARMS-qPCR检测的突变状态以及手术病理等信息。
在73份FNA样本中总共检测到71个单核苷酸变异、3个融合基因以及2个微卫星高度不稳定状态。BRAF V600E突变是这些恶性甲状腺结节中最常见的突变。在我们的研究组中，将细胞学与新一代测序检测到的基因背景相结合后，诊断敏感性从0.582（95%CI：0.441 - 0.711）提高到了0.855（95%CI：0.728 - 0.930）（P<0.001），而特异性在结合前后分别为1.000（95%CI：0.732 - 1.000）和0.857（95%CI：0.562 - 0.975）（P = 0.25），未受影响。
甲状腺结节的新一代测序仅通过细针穿刺活检就能提高术前诊断敏感性。它还能为用药指导提供基因背景。临床医生有可能将细胞学与基因改变相结合，以制定更精确的甲状腺结节诊断策略。
