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甲状腺细针抽吸中 BRAF-V600E 突变分析的实际应用:对临床决策的影响。

Real-life use of BRAF-V600E mutation analysis in thyroid nodule fine needle aspiration: consequences on clinical decision-making.

机构信息

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.

出版信息

Endocrine. 2021 Sep;73(3):625-632. doi: 10.1007/s12020-021-02693-2. Epub 2021 Mar 23.


DOI:10.1007/s12020-021-02693-2
PMID:33759074
Abstract

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.

摘要

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。

相似文献

[1]
Real-life use of BRAF-V600E mutation analysis in thyroid nodule fine needle aspiration: consequences on clinical decision-making.

Endocrine. 2021-9

[2]
BRAF mutation test on fine-needle aspiration specimens of thyroid nodules: Clinical correlations for 4600 patients.

Cancer Med. 2022-1

[3]
Value of V600E in High-Risk Thyroid Nodules with Benign Cytology Results.

AJNR Am J Neuroradiol. 2018-11-29

[4]
Comparison of the Clinical Validity of Droplet Digital PCR to ARMS-PCR for BRAF V600E Mutation Detection in Thyroid Nodules.

J Clin Lab Anal. 2020-11

[5]
[Clinical role of BRAF V600E mutation testing in thyroid nodules].

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2014-6

[6]
BRAF mutation analysis by ARMS-PCR refines thyroid nodule management.

Clin Endocrinol (Oxf). 2019-12

[7]
Fine-needle Aspiration Washout Precipitation Specimens: An Acceptable Supplement to Genetic Mutation Detection of Thyroid Nodules.

Technol Cancer Res Treat. 2021

[8]
BRAF V600E mutation analysis of thyroid nodules needle aspirates in relation to their ultrasongraphic classification: a potential guide for selection of samples for molecular analysis.

Thyroid. 2010-3

[9]
Contribution of the BRAF mutation analysis in calcified thyroid nodules.

AJR Am J Roentgenol. 2012-4

[10]
What to do with thyroid nodules showing benign cytology and BRAF(V600E) mutation? A study based on clinical and radiologic features using a highly sensitive analytic method.

Surgery. 2015-2

引用本文的文献

[1]
Intelligent diagnosis of thyroid nodules with AI ultrasound assistance and cytology classification.

Front Endocrinol (Lausanne). 2025-5-21

[2]
Deciphering the progression of fine-needle aspiration: A bibliometric analysis of thyroid nodule research.

Medicine (Baltimore). 2024-5-17

[3]
Effective Use of microRNA, BRAF and Sonographic Risk Assessment in Bethesda III Thyroid Nodules Requires a Different Approach to Nodules with Features of Nuclear Atypia and Other Types of Atypia.

Cancers (Basel). 2023-8-27

[4]
Ultrasound Parameters Can Accurately Predict the Risk of Malignancy in Patients with "Indeterminate TIR3b" Cytology Nodules: A Prospective Study.

Int J Mol Sci. 2023-5-5

[5]
Fine-needle Aspiration Washout Precipitation Specimens: An Acceptable Supplement to Genetic Mutation Detection of Thyroid Nodules.

Technol Cancer Res Treat. 2021

本文引用的文献

[1]
Testing for BRAF (V600E) Mutation in Thyroid Nodules with Fine-Needle Aspiration (FNA) Read as Suspicious for Malignancy (Bethesda V, Thy4, TIR4): a Systematic Review and Meta-analysis.

Endocr Pathol. 2020-3

[2]
Surgical Hypoparathyroidism.

Endocrinol Metab Clin North Am. 2018-10-12

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The Diagnosis and Management of Thyroid Nodules: A Review.

JAMA. 2018-3-6

[4]
Diagnostic Utility of Molecular and Imaging Biomarkers in Cytological Indeterminate Thyroid Nodules.

Endocr Rev. 2018-4-1

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Quality of life in patients with hypoparathyroidism receiving standard treatment: a systematic review.

Endocrine. 2017-8-18

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Worldwide Thyroid-Cancer Epidemic? The Increasing Impact of Overdiagnosis.

N Engl J Med. 2016-8-18

[7]
High-Resolution Melting Is a Sensitive, Cost-Effective, Time-Saving Technique for BRAF V600E Detection in Thyroid FNAB Washing Liquid: A Prospective Cohort Study.

Eur Thyroid J. 2015-6

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"Colloid-rich" follicular neoplasm/suspicious for follicular neoplasm thyroid fine-needle aspiration specimens: cytologic, histologic, and molecular basis for considering an alternate view.

Cancer Cytopathol. 2013-7-23

[9]
Does addition of BRAF V600E mutation testing modify sensitivity or specificity of the Afirma Gene Expression Classifier in cytologically indeterminate thyroid nodules?

J Clin Endocrinol Metab. 2013-3-8

[10]
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Nat Rev Endocrinol. 2011-8-30

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