Background: Thyroid neoplasms exhibit a diverse molecular landscape, and the 2022 WHO classification emphasizes the critical role of molecular profiling in thyroid cancer management; however, comprehensive mutational data from fine-needle aspiration cytology (FNAC) samples using targeted next-generation sequencing (NGS) are still limited, necessitating further investigation to guide clinical practice. Purpose: To characterize the mutational landscape of thyroid neoplasms using targeted NGS of FNAC samples and to assess the clinical implications of molecular profiling. Materials and Methods: This retrospective study included 952 patients with thyroid carcinomaneoplasms who underwent surgery at Sun Yat-sen Memorial Hospital from 2021 to 2023. Preoperative ultrasound, FNAC, and targeted NGS were performed. NGS panels covering 18, 88, and pan-cancer genes were used to analyze FNAC samples. Molecular alterations were correlated with clinical and pathological features. Results: The most frequent mutation was BRAFV600E(84.45%), followed by RET (6.41%), BRCA1/2 (4.41%) and RAS (4.41%). Patients were categorized into BRAF-like (830 cases), RAS-like (36 cases), high-risk mutations (25 cases), and other mutations (28 cases). High-risk mutations were associated with older age and larger tumor size. BRAF-like tumors had a higher lymph node metastasis rate (58.77%) compared to RAS-like tumors (33.33%). Tumor mutation burden varied significantly among different thyroid neoplasm subtypes. Conclusions: Molecular profiling using targeted NGS of FNAC samples provides valuable insights into the genetic landscape of thyroid neoplasms and has significant clinical implications for diagnosis and personalized treatment strategies. Further validation with paired tumor and plasma samples is warranted.
背景：甲状腺肿瘤表现出多样化的分子特征，2022年世界卫生组织分类强调了分子谱分析在甲状腺癌管理中的关键作用；然而，通过细针穿刺细胞学（FNAC）样本进行靶向二代测序（NGS）获得的全面突变数据仍然有限，需要进一步研究以指导临床实践。目的：利用FNAC样本的靶向NGS技术，描述甲状腺肿瘤的突变特征，并评估分子谱分析的临床意义。材料与方法：这项回顾性研究纳入了2021年至2023年在中山大学孙逸仙纪念医院接受手术的952例甲状腺肿瘤患者。术前进行了超声检查、FNAC和靶向NGS检测。使用覆盖18个、88个基因以及泛癌基因的NGS panel对FNAC样本进行分析。分子改变与临床及病理特征进行了相关性分析。结果：最常见的突变是BRAFV600E（84.45%），其次是RET（6.41%）、BRCA1/2（4.41%）和RAS（4.41%）。患者被分为BRAF样（830例）、RAS样（36例）、高风险突变（25例）和其他突变（28例）。高风险突变与年龄较大和肿瘤体积较大相关。与RAS样肿瘤（33.33%）相比，BRAF样肿瘤的淋巴结转移率更高（58.77%）。不同甲状腺肿瘤亚型之间的肿瘤突变负荷存在显著差异。结论：利用FNAC样本进行靶向NGS分子谱分析，为了解甲状腺肿瘤的遗传特征提供了宝贵信息，并对诊断和个体化治疗策略具有重要的临床意义。未来需要通过配对肿瘤组织和血浆样本进行进一步验证。
肿瘤(癌症)患者之家