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

Abstract

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, BRAFV600E 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 BRAFV600E mutation was found in 170/354 PTC patients (female = 126). Forty-two out of 170 BRAFV600E 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 BRAFV600E mutation +ve and BRAFV600E 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 BRAFV600E mutation +ve than BRAFV600E mutation −ve patients (18/42 vs. 2/22, respectively; P = 0.013). Conclusion This study suggests that BRAFV600E mutation represents a significant risk factor for developing contralateral lymph-node metastases and confirms that BRAFV600E 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.

Shared Decision Making for Radioiodine Therapy and the Actual Pattern of Care in Intermediate-Risk Differentiated Thyroid Carcinoma

“…One possible risk factor is the BRAF (V600E) mutation. Several studies have shown a correlation between the presence of this mutation and a more aggressive course (32). Elisei et al showed the BRAF (V600E) mutation as an independent poor prognostic factor for disease persistence in patients with low-risk DTC (33).…”

Translational Utility of Liquid Biopsies in Thyroid Cancer Management

“…BRAF V600E , an oncogenic mutation, is never present in benign disease, yet it is detected in about two-thirds of all differentiated thyroid cancers [ 50 ]. Assessment of BRAF V600E status is now standard in the risk stratification of PTC and an essential determinant of treatment options for anaplastic thyroid cancer (ATC) [ 51 , 52 , 53 , 54 , 55 ]. RET rearrangements are the second most common somatic alteration seen in PTC, and occur in up to 40% of PTC [ 56 ].…”