BRAF mutation analysis by ARMS-PCR refines thyroid nodule management

Fine-needle aspiration (FNA) of thyroid nodules leads to nearly 25% indeterminate nodules, while BRAF^V600E mutation helps to predicting papillary thyroid carcinoma (PTC). However, the clinical validity and utility of the BRAF^V600E mutation detected using preoperative FNA samples in a large cohort were rarely reported.

To explore the clinical significance of the BRAF^V600E mutation on preoperative diagnosis and decision-making in a large FNA cohort in China.

This was a prospective study of BRAF^V600E mutation analysis using an amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in FNA samples.

The study involved 2640 samples from 2307 patients undergoing FNA procedures in a Chinese medical centre.

A high mutation rate of 86.7% was found in the PTC population. For indeterminate thyroid nodules, the malignant rate of BRAF^V600E+ and BRAF^V600E- was 87.8% and 39.5% in the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) III, and 88.2% and 31.8% in the BSRTC IV, respectively. A cost-effective diagnostic model combining both BSRTC grading and BRAF^V600E mutation status showed the highest sensitivity of 82.9% and specificity of 85.4%. Central lymph node metastasis (CLNM) was independent of the BRAF mutation status and accounted for 34.2% of the patients with PTC. C_T values of BRAF^V600E of patients with PTMC were significantly lower in young patients and patients with CLNM.

The combined analysis of cytological results and BRAF^V600E mutation is highly recommended in BRAF^V600E high-prevalence regions, including China. Prophylactic central neck dissection should be performed in selected patients without regard to the BRAF mutation status.