诊断学理论与实践

诊断学理论与实践 ›› 2025, Vol. 24 ›› Issue (02): 187-193.doi: 10.16150/j.1671-2870.2025.02.010

• 论著 • 上一篇    下一篇

BRAFV600E 突变在甲状腺结节细胞学样本中的分布及其临床应用价值

王蕾, 金晶晶, 余纳, 肖立()   

  1. 复旦大学附属华东医院病理科，上海 200040
  • 收稿日期:2024-09-25 接受日期:2025-04-10 出版日期:2025-04-25 发布日期:2025-07-11
  • 通讯作者: 肖立 E-mail： fangjx0207@foxmail.com

Distribution of BRAFV600E mutation in cytological samples of thyroid nodules and its clinical application value

WANG Lei, JIN Jingjing, YU Na, XIAO Li()   

  1. Department of Pathology, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China
  • Received:2024-09-25 Accepted:2025-04-10 Published:2025-04-25 Online:2025-07-11

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摘要：

目的： 探讨BRAFV600E 突变在甲状腺结节细胞学诊断（fine-needle aspiration cytology， FNAC）中的分布特征，分析FNAC联合BRAFV600E 突变检测在甲状腺乳头状癌（papillary thyroid carcinoma， PTC）术前诊断中的价值。 方法： 回顾性分析2021年11月至2024年1月期间，在复旦大学附属华东医院接受甲状腺细针穿刺细胞学检查的261个连续甲状腺结节，所有结节均采用扩增阻滞突变系统-聚合酶链式反应（amplification refractory mutation system-polymerase chain reaction， ARMS-PCR）法检测BRAF、TERT、RET、HRAS、KRAS、NRAS、PPARG和NTRK基因突变。分析BRAFV600E 突变在甲状腺细胞病理学Bethesda报告系统（the Bethesda system for reporting thyroid cytopathology， TBSRTC）不同类别结节中的分布。69/261个甲状腺结节经术后病理检查，其中65个甲状腺结节诊断为PTC，余3个为滤泡性肿瘤和1个为滤泡性结节。以术后病理诊断为金标准，分析FNAC结合BRAFV600E 突变检测在术前诊断PTC的价值。 结果： 261个FNAC样本中，98个甲状腺结节BRAFV600E 阳性，78.6%的阳性样本分布于TBSRTC Ⅴ、Ⅵ类。FNAC、BRAF突变检测以及FNAC联合BRAF突变检测鉴别PTC的准确率分别为76.8%、81.2%、89.9%，灵敏度分别为76.9%、80.0%、90.8%，特异度分别为75.0%、100.0%、75.0%，各方法的受试者操作特征（receiver operator characteristic， ROC）曲线的曲线下面积（area under curve， AUC）分别为0.759 6、0.900 0、0.828 8。Z检验结果显示，FNAC结合BRAFV600E 突变检测的AUC值较FNAC有所提高（P=0.008 2）。 结论： 78.6%的BRAFV600E 突变阳性病例位于细胞学TBSRTC Ⅴ、Ⅵ类，其可作为PTC高风险结节诊断的重要补充依据。相比于FNAC单独诊断，FNAC联合BRAFV600E 突变检测可提高甲状腺乳头状癌的术前诊断准确率。

关键词: 细针穿刺细胞学, BRAFV600E 突变检测, 甲状腺乳头状癌, 诊断学

Abstract:

Objective To investigate the distribution characteristics of BRAFV600E mutation in cytological diagnosis of thyroid fine-needle aspiration cytology (FNAC) and analyze the diagnostic value of combining FNAC with BRAFV600E mutation detection for the preoperative diagnosis of papillary thyroid carcinoma (PTC). Methods A retrospective analysis was conducted on 261 consecutive thyroid nodules that underwent FNAC at Huadong Hospital Affiliated to Fudan University between November 2021 and January 2024. All nodules were tested for mutations in BRAF, TERT, RET, HRAS, KRAS, NRAS, PPARG, and NTRK genes using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The distribution of BRAFV600E mutations across the Bethesda system for reporting thyroid cytopathology (TBSRTC) was analyzed. Among the 261 thyroid nodules, 69 underwent postoperative histopathological examination, including 65 diagnosed as PTC, 3 as follicular tumors, and 1 as a follicular nodule. Using postoperative histopathology as the gold standard, the diagnostic value (accuracy, sensitivity, and specificity) of FNAC combined with BRAFV600E mutation detection for preoperative PTC diagnosis was analyzed. Results Among the 261 FNAC samples, 98 thyroid nodules were BRAFV600E -positive, with 78.6% of positive samples classified as category Ⅴ or Ⅵ in the TBSRTC. The accuracy of FNAC, BRAFV600E mutation detection, and their combination in differentiating PTC was 76.8%, 81.2%, and 89.9%, respectively. The sensitivi-ty was 76.9%, 80.0%, and 90.8%, and the specificity was 75.0%, 100.0%, and 75.0%, respectively. The area under the ROC curve (AUC) for each method was 0.759 6, 0.900 0, and 0.828 8, respectively. Z-test results showed that the AUC of FNAC combined with BRAFV600E mutation detection was improved compared to that of FNAC alone (P=0.008 2). Conclusion This study has found that 78.6% of BRAFV600E mutation-positive cases were classified as categories Ⅴ and Ⅵ in the TBSRTC, indicating that BRAFV600E mutation detection can serve as an important supplementary marker for diagno-sing high-risk PTC nodules. Compared with FNAC alone, the combination of FNAC and BRAFV600E mutation detection improves the preoperative diagnostic accuracy of PTC.

Key words: Fine-needle aspiration cytology, BRAFV600E mutation detection, Papillary thyroid carcinoma, Diagnostics

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