BRAFV600E mutation is associated with increased prevalence of contralateral lymph-node metastases in low and low-to-intermediate risk papillary thyroid cancer

Objective Papillary thyroid cancer (PTC) is the most common endocrine malignancy. Despite good prognosis being generally associated with PTC, persistent/recurrent disease can be observed in a not negligible number of patients. Accurate postoperative management can lead to a significant improvement of risk stratification/staging of PTC patients identifying those at higher risk of a more aggressive clinical course. Molecular tests were introduced at the beginning of the 2000s to improve PTC risk stratification. Methods We reviewed the records of 354/1185 patients affected by low or low-to-intermediate risk unilateral-PTC. In these patients, BRAF(V600E) mutation was looked for and 131-radioiodine therapy was performed 3 months after thyroid surgery. A radioiodine post-therapeutic imaging was obtained in all patients. Results BRAF(V600E) mutation was found in 170/354 PTC patients (female = 126). Forty-two out of 170 BRAF(V600E) mutation +ve patients (female = 27) had ipsilateral (n = 24) or contralateral (n = 18) loco-regional metastases at post-therapeutic imaging. Significant differences in terms of 2015 American Thyroid Association risk stratification, Hashimoto thyroiditis prevalence, tumor size, multifocality, disease staging and aggressive variant were observed between BRAF(V600E) mutation +ve and BRAF(V600E) mutation -ve patients (P <= 0.001;P = 0.001; P <= 0.001; P = 0.026; P <= 0.001; P <= 0.001). Interestingly, the prevalence of contralateral lymph-node metastases was significantly higher in BRAF(V600E) mutation +ve than BRAF(V600E) mutation -ve patients (18/42 vs. 2/22, respectively; P = 0.013). Conclusion This study suggests that BRAF(V600E) mutation represents a significant risk factor for developing contralateral lymph-node metastases and confirms that BRAF(V600E) mutation is associated with more aggressive PTC features and a higher prevalence of metastatic disease also in low or low-to-intermediate-risk PTC patients.