Association of BRAFV600E Mutation with the Aggressive Behavior of Papillary Thyroid Microcarcinoma: A Meta-Analysis of 33 Studies

An association between the BRAF(V600E) mutation and the clinicopathological progression of papillary thyroid microcarcinoma (PTMC) has been suggested. We aimed to summarize the relevant literature and determine the predictive value of BRAF(V600E) mutation in predicting clinical outcomes and risk stratification in patients with PTMC. A systematic search using PubMed, Cochrane, and Embase up to February 2020 was performed. A total of 33 studies met the inclusion criteria, resulting in a pool of 8838 patients, of whom 5043 (57.1%) patients were positive for BRAF(V600E) mutation. Tumors with positive BRAF(V600E) mutation had a higher tendency for multifocality (RR = 1.09, 95%CI = 1.03-1.16), extrathyroidal extension (RR = 1.79, 95%CI = 1.37-2.32), and lymph node metastasis (RR = 1.43, 95%CI = 1.19-1.71). Patients with BRAF(V600E) mutation were at increased risk of disease recurrence (RR = 1.90, 95%CI = 1.43-2.53). PTMC in patients positive for the BRAF(V600E) mutation is more aggressive than wild-type BRAF PTMC. Since BRAF-mutated PTMC is generally more resistant to radioiodine treatment, patients with BRAF(V600E)-mutated PTMC may require earlier management, such as a minimally invasive ablative intervention. Conservative management by active surveillance may be suitable for patients with wild-type BRAF(V600E) PTMC.