Clinical Implication of Highly Sensitive Detection of the BRAF V600E Mutation in Fine-Needle Aspirations of Thyroid Nodules: A Comparative Analysis of Three Molecular Assays in 4585 Consecutive Cases in a BRAF V600E Mutation-Prevalent Area

Abstract Context: Detection of the BRAF V600E mutation in fine-needle aspiration cytology (FNAC) specimens may increase the value of FNAC. Objective: The objectives of the study was to compare the diagnostic performance of BRAF assays that differ in sensitivity and to examine the associations between the BRAF V600E mutation status and the clinicopathological features in papillary thyroid carcinoma (PTC). Design and Setting: Three molecular assays were performed in all subjects and compared with regard to FNAC and histology results. Participants: We evaluated 4585 consecutive patients who were found to have malignant or indeterminate thyroid nodules by ultrasonography. Outcome Measures: All FNAC samples were tested for the BRAF V600E mutation using conventional Sanger sequencing, dual-priming oligonucleotide-PCR, and mutant enrichment with 3′-modified oligonucleotide (MEMO) sequencing. Results: The detection sensitivities of the three molecular assays for the BRAF V600E mutation were 20, 2, and 0.1%, respectively. Compared with conventional Sanger sequencing (n = 673), dual-priming oligonucleotide-PCR and MEMO sequencing detected more tumors with the BRAF V600E mutation (n = 919 and n = 1044, respectively), especially tumors with a benign, indeterminate, or nondiagnostic cytology. All BRAF-positive tumors that were histologically examined were shown to be PTC, regardless of cytology results. The clinical sensitivities of the three assays for detecting PTC were 54.8, 74.4, and 79.7%, respectively. BRAF V600E mutations in microcarcinomas (≤10 mm) were detected more efficiently as the detection sensitivity of the assay increased (P < 0.001). Tumor size correlated significantly with multifocality, extrathyroidal extension, and lymph node metastasis (P = 0.003, P < 0.001 and P < 0.001, respectively), but the BRAF V600E mutation status was not associated with any of those features. Conclusion: Highly sensitive and specific molecular assays such as MEMO sequencing are optimal for detecting the BRAF mutations in thyroid FNAC because these techniques can detect PTC that might be missed by cytology or less sensitive molecular assays.

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

Technology in Cancer Research & Treatment ◽

10.1177/15330338211057982 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110579

Author(s):

Yongmei Cui ◽

Xiangqi Huang ◽

Jinrui Guo ◽

Nana Zhang ◽

Jing Liang ◽

...

Keyword(s):

Fine Needle Aspiration ◽

Thyroid Nodules ◽

Needle Aspiration ◽

Braf V600e Mutation ◽

Braf V600e ◽

Invasive Technique ◽

Sample Type ◽

Mutation Status ◽

Fine Needle ◽

Capsule Invasion

Objectives: Thyroid nodules are common in adults, but only some of them are malignant. Ultrasound-guided fine-needle aspiration (FNA) is widely applied as a reliable and minimally invasive technique for evaluating thyroid nodules. However, the scarcity of FNA biopsy specimens poses a challenge to molecular diagnosis. This study aimed to evaluate the feasibility of FNA washout precipitation specimens as an effective supplement to the thyroid genetic test. Methods: A total of 115 patients with thyroid nodules were enrolled in our study. The BRAF V600E mutation status was detected in all FNA washout precipitation specimens and biopsy formalin-fixed paraffin-embedded (FFPE) specimens using an amplification refractory mutation system PCR (ARMS-PCR). All patients underwent cytological diagnoses; 79 patients also underwent surgery for histopathological analysis. Results: All the 115 samples were successfully analyzed using both FNA washout precipitation and biopsy FFPE specimens. The results showed that the BRAF V600E status detected in 96 FNA washout precipitation specimens were consistent with that in FNA biopsy FFPE specimens, including 41 BRAF V600E positive and 55 BRAF V600E negative, achieving a concordance rate of 84.4% (kappa = 0.689). Furthermore, the BRAF V600E mutation status using FNA washout precipitation specimens provided a 100.0% positive predictive value for diagnosing papillary thyroid carcinoma in patients with The Bethesda system for reporting thyroid cytopathology (TBSRTC) V. Besides, the BRAF V600E mutation status was positive in 90.9% (10/11) FNA washout precipitation specimens from patients with capsule invasion, achieving a higher overall sensitivity of 100.0%, compared with 57.1% of FNA washout precipitation specimens from patients without capsule invasion. Conclusion: These results suggested that FNA washout precipitation specimens might be a valuable supplementary sample type for detecting the BRAF V600E mutation in patients with thyroid nodules, especially with thyroid capsule invasion.

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Significance of BRAF V600E Mutation and Cytomorphological Features for the Optimization of Papillary Thyroid Cancer Diagnostics in Cytologically Indeterminate Thyroid Nodules

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-0588-4885 ◽

2018 ◽

Vol 127 (04) ◽

pp. 247-254 ◽

Cited By ~ 2

Author(s):

Augustas Beiša ◽

Mindaugas Kvietkauskas ◽

Virgilijus Beiša ◽

Mindaugas Stoškus ◽

Elvyra Ostanevičiūtė ◽

...

Keyword(s):

Logistic Regression ◽

Thyroid Cancer ◽

Logistic Regression Model ◽

Thyroid Nodules ◽

Needle Aspiration ◽

Braf V600e Mutation ◽

Braf V600e ◽

Papillary Thyroid ◽

Mutation Status ◽

Fine Needle

Abstract Background Ultrasound guided fine needle aspiration biopsy with cytologic analysis is an initial step in diagnostic of thyroid nodules. Unfortunately, up to 30% of biopsies are indeterminate and diagnostic surgery is required. The aim of this study was to estimate the diagnostic value of BRAF V600E mutation status combined with cytomorphological features for diagnosis of papillary thyroid cancer (PTC) in cytologically indeterminate thyroid nodules. Methods A prospective study analyzed patients who had ultrasound suspicious thyroid nodules, underwent fine needle aspiration and cytological examination, and were classified according to the Bethesda system. Patients from indeterminate diagnostic categories were examined for BRAF V600E mutation and 22 cytomorphological features, and underwent thyroid surgery. A binary logistic regression model was used to evaluate the diagnostic utility. Results A total of 219 patients met study criteria. After histological examination, 77 (35.2%) patients were diagnosed with PTC and 142 (64.8%) with benign nodular thyroid disease. According to logistic regression model, significant features for PTC diagnosis were: liquid colloid consistency, papillary structures, eosinophilic colloid bodies, and BRAF V600E mutation. Risk groups classified by this model have sensitivity of 80.5% (95% CI: 69.9 to 88.7), specificity of 99.3% (95% CI: 96.1 to 100), positive predictive value of 98.4% (95% CI: 89.8 to 99.8), negative predictive value of 90.4% (95% CI: 85.7 to 93.7), and accuracy of 92.7% (95% CI: 88.4 to 95.8) for PTC diagnosis. Conclusions Evaluation of BRAF V600E mutation status combined with cytomorphological features for diagnosis of PTC in cytologically indeterminate thyroid nodules can significantly improve diagnostic accuracy and reduce the number of diagnostic operations (calculator available at www.ptc-calc.we2host.lt).

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BRAF V600E as an accurate marker to complement fine needle aspiration (FNA) cytology in the guidance of thyroid surgery in the Chinese population: evidence from over 1000 consecutive FNAs with follow-up

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyaa209 ◽

2020 ◽

Author(s):

Qunzi Zhao ◽

Yong Wang ◽

Qin Ye ◽

Ping Wang ◽

Jianyu Rao

Keyword(s):

Fine Needle Aspiration ◽

Thyroid Surgery ◽

Chinese Population ◽

Thyroid Nodules ◽

Needle Aspiration ◽

Braf V600e Mutation ◽

Braf V600e ◽

Histopathological Diagnosis ◽

Fine Needle ◽

Specificity And Sensitivity

Abstract Background Currently, several commercial molecular tests have been developed for reclassifying thyroid nodules with indeterminate fine needle aspiration cytology. These tests are quite expensive and not available in China. Previous studies demonstrated a very high prevalence of the BRAF V600E mutation in Asian people. A high incidence may result in a robust sensitivity. We conducted this study to determine the prevalence of BRAF V600E mutation and its ability to reclassify cytologically indeterminate thyroid nodules in the Chinese population. Methods Between January 2016 and October 2018, consecutive patients who underwent a fine needle aspiration procedure and agreed to provide materials for molecular analysis in our hospital were recruited in this study. All were followed up until they had a thyroidectomy and a final pathological diagnosis or until January 2019 (those did not have surgery). Results A total of 1960 patients were included in this study. Until January 2019, 1240 patients underwent surgery. Using histopathological diagnosis as a gold standard, the overall sensitivity and specificity of the BRAF V600E mutational analysis for the discrimination of benign nodules from cancer in thyroid fine needle aspiration samples were 83.3% (81.0–85.3%) and 96.0% (77.7–99.8%), respectively, with an area under the ROC curve of 0.90 (95% CI 0.85–0.95, P < 0.001). Among cases with indeterminate cytology, BRAF-positive cases were showing malignancy in the final pathology, and BRAF-negative cases were showing safer to be followed up. Conclusion The BRAF V600E mutation is highly prevalent in the Chinese population and can accurately complement cytopathology in the guidance of thyroid surgery. Mini-abstract: The BRAF V600E mutation has both high specificity and sensitivity to predict thyroid malignancy in the Chinese population. It can accurately complement cytopathology in the guidance of thyroid surgery.

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