BRAF mutation analysis by ARMS-PCR refines thyroid nodule management
BRAF mutation analysis by ARMS-PCR refines thyroid nodule management
复制标题
通过 ARMS-PCR 进行 BRAF 突变分析改进甲状腺结节管理
DOI：
10.1111/cen.14079
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发表时间：
2019-10-01
影响因子：
3.2
通讯作者：
Zheng, Bing
中科院分区：
文献类型：
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作者：
Li, Xinyang;Li, Enling;Zheng, Bing
甲状腺结节细针穿刺（FNA）导致近25%的结节不确定，而BRAF（V600 E）突变有助于预测甲状腺乳头状癌（PTC）。然而，在一个大的队列中使用术前FNA样本检测BRAF（V600 E）突变的临床有效性和实用性很少报道。目的探讨BRAF（V600 E）基因突变在中国大样本FNA术前诊断和决策中的临床意义。设计：本研究采用扩增难治性突变系统-聚合酶链反应（ARMS-PCR）对FNA样本进行BRAF（V600 E）突变分析。该研究涉及2640个样本，来自2307名在中国医疗中心接受FNA手术的患者。结果PTC人群中的突变率高达86.7%。BSRTC Ⅲ型和Ⅳ型中，BRAF（V600 E+）和BRAF（V600 E-）的恶性率分别为87.8%和39.5%和88.2%和31.8%。结合BSRTC分级和BRAF（V600 E）突变状态的成本效益诊断模型显示最高的敏感性为82.9%，特异性为85.4%。中心淋巴结转移（CLNM）与BRAF突变状态无关，占PTC患者的34.2%。PTMC患者的BRAF（V600 E）C-T值明显低于青年患者和CLNM患者。结论在BRAF（V600 E）高流行地区，包括中国，应结合细胞学检查结果和BRAF（V600 E）基因突变进行分析。应在选定的患者中进行预防性中央颈清扫术，而不考虑BRAF突变状态。
Background Fine-needle aspiration (FNA) of thyroid nodules leads to nearly 25% indeterminate nodules, while BRAF(V600E) mutation helps to predicting papillary thyroid carcinoma (PTC). However, the clinical validity and utility of the BRAF(V600E) mutation detected using preoperative FNA samples in a large cohort were rarely reported. Aim To explore the clinical significance of the BRAF(V600E) mutation on preoperative diagnosis and decision-making in a large FNA cohort in China. Design This was a prospective study of BRAF(V600E) mutation analysis using an amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in FNA samples. Patients The study involved 2640 samples from 2307 patients undergoing FNA procedures in a Chinese medical centre. Results A high mutation rate of 86.7% was found in the PTC population. For indeterminate thyroid nodules, the malignant rate of BRAF(V600E+) and BRAF(V600E-) was 87.8% and 39.5% in the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) III, and 88.2% and 31.8% in the BSRTC IV, respectively. A cost-effective diagnostic model combining both BSRTC grading and BRAF(V600E) mutation status showed the highest sensitivity of 82.9% and specificity of 85.4%. Central lymph node metastasis (CLNM) was independent of the BRAF mutation status and accounted for 34.2% of the patients with PTC. C-T values of BRAF(V600E) of patients with PTMC were significantly lower in young patients and patients with CLNM. Conclusions The combined analysis of cytological results and BRAF(V600E) mutation is highly recommended in BRAF(V600E) high-prevalence regions, including China. Prophylactic central neck dissection should be performed in selected patients without regard to the BRAF mutation status.