TheBRAFV600E Mutation Is an Independent, Poor Prognostic Factor for the Outcome of Patients with Low-Risk Intrathyroid Papillary Thyroid Carcinoma: Single-Institution Results from a Large Cohort Study

The BRAF(V600E) mutation, the most frequent genetic alteration in papillary thyroid carcinoma (PTC), was demonstrated to be a poor prognostic factor. The aim of this study was to evaluate its prognostic significance in a large cohort of low-risk intrathyroid PTC.Among the 431 consecutive PTC patients, we selected 319 patients with an intrathyroid tumor and no metastases (T1-T2, N0, M0). The BRAF(V600E) mutation was analyzed by PCR-single-strand conformation polymorphism analysis and direct genomic sequencing. The correlation between the presence/absence of the mutation, the clinical-pathological features, and the outcome of the PTC patients was investigated.The BRAF(V600E) mutation was present in 106 of 319 PTC patients (33.2%). Its prevalence was also the same in subgroups identified according to the level of risk. The BRAF(V600E) mutation correlated with multifocality, aggressive variant, absence, or infiltration of the tumoral capsule. BRAF(V600E)-mutated PTC also required a higher number of radioiodine courses to obtain disease-free status. The BRAF(V600E) mutation was the only prognostic factor predicting the persistence of the disease in these patients after 5 yr of follow-up.The BRAF(V600E) mutation was demonstrated to be a poor prognostic factor for the persistence of the disease independent from other clinical-pathological features in low-risk intrathyroid PTC patients. It could be useful to search for the BRAF(V600E) mutation in the workup of low-risk PTC patients to distinguish those who require less or more aggressive treatments. In particular, the high negative predictive value of the BRAF(V600E) mutation could be useful to identify, among low-risk PTC patients, those who could avoid 131-I treatment.