To determine the clinicopathological implication of BRAF-V600^E mutation in thyroid papillary carcinoma (PTC) .

The clinical data of 331 patients diagnosed with PTC between January 2016 and March 2019 in Department of Thyroid Surgery, Guangzhou First People’s Hospital, were analyzed retrospectively. Detection for the BRAF-V600^E mutation was completed by amplification refractory mutation system (ARMS) using quantitative real-time PCR (RT-PCR) . According to the 8th edition of the American Joint Committee on Cancer (AJCC) age risk stratification, the patients were divided into the <55-year-old group and the ≥55-year-old group with age cut-off value of 55 years. The relationship between BRAF-V600 ^E mutation and clinicopathological characteristics was analyzed by χ² test or Fisher's exact test. Multivariate Cox regression analysis was used to analyze the risk of tumor recurrence in two groups of patients. Recurrence-free survival rate (RFS) was analyzed using the Kaplan-Meier method.

The BRAF-V600^E mutation was detected in 236 of 331 (71.3%) PTC patients. The<55-year-old group comprised 210 PTC patients, among which, BRAF-V600^E mutation was detected in 145 (69.0%) , and was associated with Hashimoto's thyroiditis, histological subtype, lymph node metastasis, Radioactive iodine (RAI) dose, moderate/high recurrence risk, and T staging (allP<0.05) . The ≥55-year-old group comprised 121 PTC patients, among which, BRAF-V600^E mutation was detected in 91 (75.2%) , and was associated with tumor size, Hashimoto's thyroiditis, histological subtype, RAI dose, moderate/high recurrence risk, T and N stagings, and AJCC stages Ⅲ/Ⅳ (allP<0.05) . BRAF-V600^E mutation was not an independent predictor of tumorrecurrencein the <55-year-old group. However, in the ≥55-year-old group, BRAF-V600 ^E mutation, male, multiple lesions, N and M stagings were part of Cox regression equation, and were all related to the recurrence of PTC (all P<0.05) . Themedian RFS and 5-yeartumor-free survival rate was 43.4 months and 62.1% in the ≥55-year-old group, compared with 78.7 months and 88.2% in the <55-year-old group, respectively. In the <55-year-old group, the BRAF-V600^E mutated and wild-type subjects did not differ in tumor-free survival curve (P=0.334) , but they differ significantly in recurrence-free survival curve (P<0.05) , with the median RFS and 5-year tumor-free survival rate being 13 months and 35.5% for the mutated subjects; 101.3 months and 92.2% for the wild-type subjects. There were no statistically significant differences in recurrence survival between the BRAF-V600^E mutatedand wild-type PTC patients who had lymph node metastasis (LNM) , either in <55 or ≥55-year-old group (both P>0.05) .

The BRAF-V600^E mutation was found to better predict aggressive and recurrent PTC based on age stratification with the cut-off of 55 years. The synergistic interaction between BRAF-V600^E mutation and age stratification may help improve clinical and diagnosis and treatment of PTC, and decision on more effective treatment protocols.

Thyroid neoplasms; Papilloma; BRAF gene; Mutation; Age distribution; Prognosis; Recurrence