Prognostic implication of BRAF and TERT promoter mutation combination in papillary thyroid carcinoma-A meta-analysis

Introduction: The use of molecular markers, especially BRAF and TERT promoter mutations, for risk stratification in papillary thyroid carcinoma (PTC) is subject to continuing debate. In this study, we aimed to investigate the clinicopathological implication of each genotype when combining BRAF and TERT promoter mutations in PTCs. Methods: We searched four electronic databases including PubMed, Scopus, Web of Science and Virtual Health Library for relevant studies. Pooled estimates of odds ratios and corresponding 95% confidence intervals were calculated using random-effect model. Results: From 111 results, we finally included 11 studies with 3911 PTC patients for meta-analyses. Our results demonstrated that PTCs with concurrent BRAF and TERT promoter mutations were associated with increased tumour aggressiveness in comparison with PTCs harbouring BRAF or TERT promoter mutation alone. The combination of BRAF and TERT promoter mutations could classify PTCs into four distinct risk groups with decreasing aggressiveness as follows: coexisting BRAF and TERT > TERT alone=BRAF alone > no mutations. Conclusion: The risk stratification of PTC based on these four genotypes can help improve the clinical management of PTCs by identifying the group of PTCs with the highest aggressiveness.