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.
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.
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.
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).
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.
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。
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。
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）。
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。
