Prognostic Value of BRAF V600E Mutation in Papillary Thyroid Carcinoma: A Meta-Analysis of Nodal Involvement, Distant Metastases, Recurrence, and Mortality.

OBJECTIVE

To investigate the prognostic value of the B-type Raf kinase (BRAF) V600E mutation in papillary thyroid carcinoma.

METHODS

A comprehensive search of PubMed/MEDLINE, Scopus, and Web of Science up to August 31, 2025 identified 46 eligible studies including 20,570 patients, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Quality Assessment of Diagnostic Accuracy Studies version 2 quality assessment. Random-effects models were applied to evaluate associations between BRAF status and major oncological outcomes.

RESULTS

BRAF V600E mutation was significantly associated with lymph node metastasis (odds ratios [OR] = 1.38; 95% confidence interval [CI], 1.17-1.61) and showed a borderline association with recurrence risk (OR = 1.56; 95% CI, 1.00-2.41). In contrast, no significant associations were observed for distant metastases (OR = 0.75; 95% CI, 0.48-1.17) or cancer-related mortality (OR = 0.97; 95% CI, 0.64-1.49). Sensitivity analyses confirmed the robustness of all pooled estimates. Meta-regressions revealed an inverse relationship between BRAF mutation prevalence and its prognostic impact, suggesting that the higher the mutation prevalence in a population, the lower its discriminative prognostic power. Funnel plot inspection and Egger's tests indicated no major publication bias.

CONCLUSION

Overall, these findings confirm that BRAF V600E mutation is associated with an increased risk of nodal metastasis and recurrence in papillary thyroid carcinoma. However, its lack of impact on distant metastases and disease-specific mortality limits its role as an independent prognostic marker in clinical decision-making.