细针穿刺样本BRAF基因突变检测在甲状腺结节风险分层管理中的应用价值

Application value of BRAF gene mutation detection in fine needle aspiration samples in risk stratification of thyroid nodules

关键词:  细针穿刺细胞学  BRAF基因  V600E突变  甲状腺结节

Key words:  fine needle aspiration cytology  BRAF gene  V600E mutation  thyroid nodule

摘要:

目的　探讨甲状腺细针穿刺（fine needle aspiration，FNA）样本的BRAF V600E基因突变检测在甲状腺结节术前风险分层管理中的应用价值。　方法　收集甲状腺结节患者手术前经超声引导下细针穿刺（ultrasound guided fine needle aspiration，US-FNA）样本141例（155个结节），用实时荧光定量PCR（quantitative real-time PCR，Q-PCR）方法检测FNA样本的BRAF V600E突变情况，同时对US-FNA样本行液基细胞薄层制片、细胞病理学诊断；以术后病理诊断结果为金标准，比较FNA样本BRAF V600E突变检测与术后病理诊断的一致性，并分析FNA样本BRAF V600E突变检测和细胞学检查两种方法在甲状腺结节术前风险分层管理中的优劣。　结果　141例（155个结节）术前FNA样本BRAF V600E突变检测结果显示BRAF V600E突变阳性率为79.4%（123/155）；与术后病理诊断结果比较，FNA样本BRAF V600E突变检测对甲状腺乳头状癌诊断敏感性87.9%、特异性100%、阳性预测值100%、阴性预测值45.2%、准确性89%。FNA细胞学检查对其诊断的敏感性87.9%、特异性78.6%、阳性预测值97.6%、阴性预测值39.3%、准确性87%。BRAF V600E突变检测联合FNA细胞学检查对甲状腺结节良恶性诊断的敏感性94.3%，与单一FNA样本BRAF V600E突变检测和细胞学检查方法的敏感性比较，差异具有统计学意义（P＜0.05）。　结论　甲状腺FNA样本BRAF V600E突变检测联合细胞学检查可作为第一推荐纳入甲状腺结节风险分层管理措施中。

Abstract:

Objective　To study the value of BRAF V600E gene mutation detection in fine needle aspiration (FNA) samples in preoperative risk stratification management of thyroid nodules. Methods　Ultrasound guided fine needle aspiration (US-FNA) samples were collected from 141 patients (155 nodules) with thyroid nodules. BRAF V600E mutation in FNA samples was detected by quantitative real-time PCR (Q-PCR). At the same time, the US-FNA samples were processed for liquid-based cell thin-layer preparation and cytopathological examination. Taking the postoperative pathological diagnosis results as the gold standard, the consistency between BRAF V600E mutation detection in FNA samples and postoperative pathological diagnosis was compared. The advantages and disadvantages of BRAF V600E mutation detection and cytology in preoperative risk stratification management of thyroid nodules were analyzed. Results　BRAF V600E mutation analysis in 141 preoperative FNA samples revealed a BRAF V600E mutation positive rate of 79.4% (123/155 nodules). In comparison with the postoperative pathological diagnosis, the sensitivity (87.9%), specificity (100%), positive predictive value (100%), negative predictive value (45.2%) and accuracy (89%) of BRAF V600E mutation detection in FNA samples in the diagnosis of thyroid papillary carcinoma were determined, as well as the sensitivity (87.9%), specificity (78.6%), positive predictive value (97.6%), negative predictive value (39.3%) and accuracy (87%) of FNA cytological diagnosis. The sensitivity of BRAF V600E mutation detection combined with FNA cytology in the diagnosis of benign and malignant thyroid nodules was 94.3%. Compared with the sensitivity of BRAF V600E mutation detection or cytology alone in a single FNA sample, the difference was statistically significant（P＜0.05）. Conclusion　BRAF V600E mutation detection combined with cytology in thyroid fine needle aspiration samples should be included in the risk stratification management measures of thyroid nodules as the first recommendation.