Dataset Information

BRAF^V600E mutation test on fine-needle aspiration specimens of thyroid nodules: Clinical correlations for 4600 patients.

ABSTRACT:

Background

The BRAF^V600E mutation is valuable for the diagnosis, prognosis, and therapy of papillary thyroid cancer (PTC). However, studies related to this mutation have involved only a small number of patients. Therefore, we performed a large-scale analysis from a single institute to evaluate the accuracy of combined fine-needle aspiration (FNA) and BRAF^V600E mutation tests for PTC diagnosis.

Methods

A total of 4600 patients with thyroid nodules who underwent both FNA cytology and BRAF^V600E mutation analysis on FNA specimens were enrolled. The association between the BRAF^V600E mutation and clinicopathological features was analyzed. A separate analysis was performed for the 311 patients who underwent repeated FNA for comparison of cytological evaluation and BRAF^V600E mutation results. The diagnostic efficacy of the BRAF^V600E mutation test and cytologic diagnoses was evaluated for 516 patients who underwent preoperative FNA tests in comparison with conclusive postoperative histopathologic results.

Results

The cytology results of all 4600 FNA samples were categorized according to The Bethesda System for Reporting Thyroid Cytology (TBSRTC) stages I-VI, which accounted for 11.76%, 60.02%, 6.46%, 3.61%, 6.71%, and 11.43% of the samples, respectively. The BRAF^V600E mutation was detected in 762 (16.57%) FNA samples, with rates of 1.48%, 0.87%, 20.20%, 3.01%, 66.02%, and 87.81% for TBSRTC I-VI lesions, respectively. Among the 311 repeat FNA cases, 81.0% of the BRAF^V600E -positive and 4.3% of the BRAF^V600E -negative specimens with an initial indication of cytological non-malignancy were ultimately diagnosed as malignant by repeat FNA (p < 0.001). Among the 516 patients who underwent thyroidectomy, the sensitivity and specificity of the BRAF^V600E mutation test alone for PTC diagnosis were 76.71% and 100.0%, respectively, which increased to 96.62% and 88.03%, respectively, when combining the BRAF^V600E mutation test with cytology. BRAF^V600E mutation was significantly associated with lymph node metastasis (p < 0.001), but not with age, gender, or tumor size.

Conclusions

The BRAF^V600E mutation test in FNA samples has potential to reduce false negatives in PTC diagnosis, and therefore plays an important role in the diagnosis of thyroid nodules, especially those with an indeterminate or nondiagnostic cytology, which should be considered for repeat FNA.

SUBMITTER: Chen H

PROVIDER: S-EPMC8704181 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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.

Project description:ImportanceThyroid cancer, predominantly papillary thyroid carcinoma (PTC), is common, but an estimated 30% of ultrasonography-guided fine-needle aspiration (FNA) biopsies of thyroid nodules are indeterminate. BRAF variation, associated with poor clinicopathological characteristics, is a useful molecular marker for diagnostics.ObjectiveTo develop a sensitive molecular assay for BRAF V600E detection in remaining tissue of thyroid FNA biopsies to identify patients with cancer carrying a BRAF variation.Design, setting, and participantsThis diagnostic study used tumor tissue from surgical formalin-fixed, paraffin-embedded (FFPE) specimens and residual tissue from thyroid FNA biopsies for genomic DNA extraction. FFPE specimens served as the validation set, and residual tissue from FNA biopsies served as the test set. A molecular assay was developed for accurate detection of BRAF V600E variation using locked nucleic acid (LNA) probe-based droplet digital polymerase chain reaction (dPCR), and the assay was validated by BRAF V600E immunohistochemical staining (IHC). The study was conducted between February 2019 and May 2021.ResultsA total of 271 specimens, including 77 FFPE specimens (with a follow-up of 48 matched surgical specimens) and 146 residual FNA samples, were collected from 223 patients (mean [SD] age, 53.8 [15.3] years; 174 [78.0%] women; 49 [22.0%] men). The molecular assay by dPCR was first established to specifically and accurately detect and quantify wild-type BRAF and variant BRAF in DNA from human follicular thyroid carcinoma-derived FTC-133 and papillary thyroid carcinoma-derived BCPAP cells. The linearity of quantification of BRAF V600E was calculated (y = 0.7339x; R2 = 0.9996) with sensitivity at 0.02 copies/μL and reproducibility in detecting variant DNA at various dilutions(coefficient of variance in 0.3% DNA, 9.63%; coefficient of variance in 1.0% DNA, 7.41%). In validation testing, the dPCR assay and IHC staining exhibited 100% specificity in concordantly identifying BRAF V600E in PTCs (κ = 0.873; P < .001) and sensitivity of 32.0% (95% CI, 19.1% to 44.9%) in dPCR and 26.0% (95% CI, 13.1% to 38.9%) in IHC staining, with an improvement by 23.08% in dPCR compared with the IHC staining. The dPCR assay further detected BRAF V600E in 39 of 146 residual FNA specimens (26.7%). At short-term follow-up, 48 patients, including 14 of 39 patients with BRAF variation and 34 of 107 patients without BRAF variation on residual FNA specimens, underwent resection. The dPCR assay of BRAF status in the matched surgical specimens showed BRAF V600E variations in 12 patients and wild-type BRAF in 36 patients, with a high agreement to that in residual tissue of FNA specimens (κ = 0.789; P < .001). Among 14 patients with BRAF variations on residual FNA, 13 were diagnosed with PTC and 1 was diagnosed with anaplastic thyroid cancer at the thyroidectomy.Conclusions and relevanceThis diagnostic study developed a sensitive molecular assay for detection and quantification of BRAF V600E variation in residual tissue from thyroid FNA biopsies to identify patients with cancer harboring BRAF V600E in a cost-effective manner, highlighting the clinical value of molecular assay of the remaining FNA tissue in the management of thyroid nodules.

Dataset Information

BRAF^V600E mutation test on fine-needle aspiration specimens of thyroid nodules: Clinical correlations for 4600 patients.

Background

Methods

Results

Conclusions

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Dataset Information

BRAFV600E mutation test on fine-needle aspiration specimens of thyroid nodules: Clinical correlations for 4600 patients.

Background

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

BRAF^V600E mutation test on fine-needle aspiration specimens of thyroid nodules: Clinical correlations for 4600 patients.