Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy.
Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy.
Endocrine. 2021 Sep;73(3):625-632. doi: 10.1007/s12020-021-02693-2. Epub 2021 Mar 23.
PURPOSE: This study aimed to evaluate the real-life use of BRAF-V600E mutation analysis in washout liquid from thyroid nodule fine needle aspiration (FNA), and the consequences of genetic result on clinical decision-making. METHODS: We retrospectively considered subjects tested for BRAF-V600E among those attending the Endocrinology Unit of Modena for FNA between 2014 and 2018. Washing fluid was collected together with cytological sample and stored at -20 °C. If the clinician deemed it necessary, the sample was thawed, DNA extracted, and genetic test performed by high-resolution melting technique. We collected data on cytology according to the Italian Consensus for the cytological classification of thyroid nodules, type of surgery (when performed), histology, and adverse events. RESULTS: Out of 7112 subjects submitted to FNA, BRAF analysis was requested for 683 (9.6%). Overall, 896 nodules were analyzed: 74% were indeterminate at cytology, mainly TIR3A (low risk). Twenty-two nodules were mutant (BRAF+). Only 2% of indeterminate, mainly TIR3B, were BRAF+. Based on final histological diagnosis, BRAF test had high specificity (100%) but poor sensitivity (21%), also in indeterminate nodules. Mutant subjects underwent more extensive surgery compared to wild type (p = 0.000), with frequent prophylactic central lymph node dissection. One third had local metastases. Higher prevalence of hypoparathyroidism was found in BRAF+ compared to wild type (p = 0.018). CONCLUSIONS: The analysis of BRAF-V600E outside of gene panels has low sensitivity, especially in indeterminate nodules, and a positive result could lead to more extensive surgery with greater risk of hypoparathyroidism and questionable clinical utility.
目的:本研究旨在评估 BRAF-V600E 突变分析在甲状腺结节细针抽吸(FNA)洗脱液中的实际应用,以及遗传结果对临床决策的影响。
方法:我们回顾性地考虑了 2014 年至 2018 年期间在摩德纳内分泌科接受 FNA 的患者中进行 BRAF-V600E 检测的患者。洗脱液与细胞学样本一起收集并存放在-20°C。如果临床医生认为有必要,将样本解冻,提取 DNA,并通过高分辨率熔解技术进行基因检测。我们根据意大利甲状腺结节细胞学分类共识收集了细胞学数据、手术类型(如果进行)、组织学和不良事件。
结果:在 7112 例接受 FNA 的患者中,有 683 例(9.6%)要求进行 BRAF 分析。总体而言,分析了 896 个结节:74%的细胞学结果为不确定,主要为 TIR3A(低风险)。22 个结节为突变型(BRAF+)。仅 2%的不确定结节(主要为 TIR3B)为 BRAF+。根据最终的组织学诊断,BRAF 检测具有很高的特异性(100%),但敏感性较低(21%),在不确定的结节中也是如此。突变患者与野生型患者相比,接受了更广泛的手术(p=0.000),且经常预防性进行中央淋巴结清扫。三分之一的患者发生局部转移。BRAF+患者的甲状旁腺功能减退症发生率高于野生型(p=0.018)。
结论:BRAF-V600E 在外显子组分析之外的分析敏感性较低,尤其是在不确定的结节中,阳性结果可能导致更广泛的手术,增加甲状旁腺功能减退症的风险,并对临床实用性提出质疑。
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