Risk and Prognostic Factors for BRAFV600E Mutations in Papillary Thyroid Carcinoma

Abstract

Background. Over the past ten years, the incidence rate of papillary thyroid carcinoma (PTC) worldwide has been increasing rapidly year by year, with the incidence rate increasing 6% annually. PTC has become the malignant tumor with the highest growth rate in the world that fourteen PTC-related mutant genes have been identified. Whether the BRAFV600E mutation related to more aggressive clinicopathologic features and worse outcome in PTC remains variable and controversial. We aim to investigate the risk factors that may predict the BRAFV600E mutation potential of these lesions and new prevention strategies in PTC patients. Methods. A total of 9,908 papillary thyroid carcinoma patients with average 74.6% BRAFV600E mutations were analyzed (RevMan 5.3 software) in this study. The PubMed, Embase, and ISI Web of Science databases were systematically searched for works published through December 15, 2021. Results. The following variables were associated with an increased risk of BRAFV600E mutation in PTC patients: $\text{age}\ge 45$ years ( $\text{OR}=1.39$ , $95\%\text{CI}=1.21–1.60$ , $p<0.00001$ ), male gender ( $\text{OR}=1.13$ , $95\%\text{CI}=0.99–1.28$ , $p=0.06$ ), multifocality ( $\text{OR}=1.22$ , $95\%\text{CI}=1.07–1.40$ , $p=0.004$ ), lymph node metastasis ( $\text{OR}=1.33$ , $95\%\text{CI}=0.79–2.23$ , $p=0.28$ ), extrathyroidal extension + ( $\text{OR}=1.61$ , $95\%\text{CI}=1.06–2.44$ , $p=0.03$ ), vascular invasion + ( $\text{OR}=2.04$ , $95\%\text{CI}=1.32–3.15$ , $p=0.001$ ), and tumor node metastasis stage ( $\text{OR}=1.61$ , $95\%\text{CI}=1.38–1.88$ , $p<0.00001$ ). In addition, tumor size (>1 cm) ( $\text{OR}=0.51$ , $95\%\text{CI}=0.32–0.81$ , $p=0.005$ ) and distant metastasis ( $\text{OR}=0.69$ , $95\%\text{CI}=0.22–2.21$ , $p=0.54$ ) had no association or risk with BRAFV600E mutation in PTC patients. Conclusion. Our systematic review identified the following significant risk factors of BRAFV600E mutation in PTC patients: age (≥45 years), gender (male), multifocality, lymph node metastasis, vascular invasion, extrathyroidal extension, and advanced tumor node metastasis stage (stages III and IV). Tumor size (>1 cm) and distant metastasis do not appear to be correlated with BRAFV600E mutation in PTC patients.