Prediction of Occult Central Lymph Node Metastasis in Papillary Thyroid Carcinoma by Preoperative BRAF Analysis Using Fine-Needle Aspiration Biopsy: A Prospective Study

Abstract

Few reports have determined whether preoperative detection of the BRAF V600E mutation in fine-needle aspiration biopsy (FNAB) may influence determination of surgical extent such as prophylactic central lymph node dissection (CLND) in patients with papillary thyroid carcinoma (PTC). Our objectives were to investigate whether preoperative BRAF analysis may assist determination of surgical extent, including prophylactic CLND with variable clinicopathological risk factors for central lymph node metastasis, in patients with PTC and clinically node-negative neck. From July 2009 to May 2011, we prospectively enrolled 148 PTC patients with clinically node-negative neck who received a total thyroidectomy and prophylactic CLND. BRAF mutation by pyrosequencing was tested on preoperative FNAB specimens. The relationships between occult central lymph node metastasis and preoperative BRAF mutation or clinicopathological factors were analyzed. Additionally, we assessed the associations between preoperative BRAF mutation status and various clinicopathological characteristics of PTC revealed postoperatively. The prevalence of the BRAF V600E mutation was 53.4%, and the rate of occult central lymph node metastasis was 25.7%. Multivariate analysis showed that tumor size over 1 cm [P = 0.006; odds ratio (OR) = 3.559], perithyroidal invasion (P = 0.023; OR = 2.893), and preoperative positive BRAF mutation (P = 0.029; OR = 2.727) were independent risk factors for the presence of occult central lymph node metastasis. BRAF mutation examined in FNAB specimens, compared with the wild-type allele, strongly predicted perithyroidal invasion (48 vs. 29%; P = 0.017), extracapsular spread (65 vs. 45%; P = 0.017), occult central lymph node metastasis (35 vs. 15%; P = 0.004), and advanced TNM stage (44 vs. 28%; P = 0.035). In the multivariate analysis, patients with preoperative positive BRAF mutation were significantly more likely (P = 0.023; OR = 2.848) to have occult central lymph node metastasis. Preoperative BRAF analysis by FNAB and primary tumor size based on ultrasonography may assist in predicting occult central lymph node metastasis in patients with PTC and clinically node-negative neck.