Ren Min, Yao Qianlan, Bao Longlong, Wang Zhiting, Wei Ran, Bai Qianming, Ping Bo, Chang Cai, Wang Yu, Zhou Xiaoyan, Zhu Xiaoli
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Eur Thyroid J. 2022 May 27;11(3):e210124. doi: 10.1530/ETJ-21-0124.
The data regarding the mutation landscape in Chinese patients with thyroid cancer are limited. The diagnostic performance of thyroid nodules by fine-needle aspiration (FNA) cytology needs optimization, especially in indeterminate nodules.
A total of 1039 FNA and surgical resection samples tested using the targeted multigene next-generation sequencing (NGS) panel were retrospectively collected. The features of gene alterations in different thyroid tumors were analyzed, and the diagnostic efficacy was evaluated.
Among 1039 samples, there were 822 FNA and 217 surgical FFPE samples. Among 207 malignant thyroid resections, a total of 181 out of 193 papillary thyroid carcinomas (PTCs) were NGS-positive (93.8%), with a high prevalence of BRAF mutations (81.9%, 158/193) and a low prevalence of RAS (1.0%, 2/193) and TERT promoter mutations (3.6%, 7/193). Gene fusions, involving the RET and NTRK3 genes, were present in 20 PTCs (10.4%) and mutually exclusive with other driver mutations. Two of three follicular thyroid carcinomas harbored multiple mutations. RET gene point mutations were common in medullary thyroid carcinoma (8/11, 72.7%). The combination of cytology and DNA-RNA-based NGS analysis demonstrated superior diagnostic value (98.0%) in FNA samples. For indeterminate thyroid nodules, the diagnostic sensitivity and specificity of NGS testing were 79.2 (38/48) and 80.0% (8/10), respectively. Two mutation-positive benign cases harbored NRAS and TSHR mutations, respectively.
Our study revealed the distinct molecular profile of thyroid tumors in the Chinese population. The combination of NGS testing and FNA cytology could facilitate the accurate diagnosis of thyroid nodules, especially for indeterminate nodules.
关于中国甲状腺癌患者突变图谱的数据有限。细针穿刺（FNA）细胞学检查对甲状腺结节的诊断性能需要优化，尤其是在不确定结节方面。
回顾性收集了总共1039份使用靶向多基因下一代测序（NGS）面板检测的FNA和手术切除样本。分析了不同甲状腺肿瘤中基因改变的特征，并评估了诊断效能。
在1039份样本中，有822份FNA样本和217份手术FFPE样本。在207例甲状腺恶性切除病例中，193例乳头状甲状腺癌（PTC）中有181例NGS呈阳性（93.8%），BRAF突变发生率高（81.9%，158/193），RAS（1.0%，2/193）和TERT启动子突变发生率低（3.6%，7/193）。涉及RET和NTRK3基因的基因融合存在于20例PTC中（10.4%），且与其他驱动突变相互排斥。三例滤泡状甲状腺癌中有两例存在多个突变。RET基因点突变在甲状腺髓样癌中常见（8/11，72.7%）。细胞学与基于DNA-RNA的NGS分析相结合在FNA样本中显示出更高的诊断价值（98.0%）。对于不确定的甲状腺结节，NGS检测的诊断敏感性和特异性分别为79.2（38/48）和80.0%（8/10）。两例突变阳性的良性病例分别携带NRAS和TSHR突变。
我们的研究揭示了中国人群甲状腺肿瘤独特的分子特征。NGS检测与FNA细胞学相结合可促进甲状腺结节的准确诊断，尤其是对于不确定结节。
