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: age ≥ 45 years ( OR = 1.39 , 95 % CI = 1.21 – 1.60 , p < 0.00001 ), male gender ( OR = 1.13 , 95 % CI = 0.99 – 1.28 , p = 0.06 ), multifocality ( OR = 1.22 , 95 % CI = 1.07 – 1.40 , p = 0.004 ), lymph node metastasis ( OR = 1.33 , 95 % CI = 0.79 – 2.23 , p = 0.28 ), extrathyroidal extension + ( OR = 1.61 , 95 % CI = 1.06 – 2.44 , p = 0.03 ), vascular invasion + ( OR = 2.04 , 95 % CI = 1.32 – 3.15 , p = 0.001 ), and tumor node metastasis stage ( OR = 1.61 , 95 % CI = 1.38 – 1.88 , p < 0.00001 ). In addition, tumor size (>1 cm) ( OR = 0.51 , 95 % CI = 0.32 – 0.81 , p = 0.005 ) and distant metastasis ( OR = 0.69 , 95 % 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.

Combined expression of the BRAFV600E mutation and PD-L1 in early papillary thyroid carcinoma and its relationship with clinicopathological features and recurrence—a retrospective cohort study

“…The included cases were TNM stage I to stage II, which are relatively early stages. A recent meta-analysis of 9,908 patients with PTC ( 16 ) indicated that late TNM staging (stage III and IV) was an important risk factor for the BRAF V600E mutation in PTC patients. Additionally, the results of this study also indicated that there was no association between or increased risk for tumor size >1 cm and the BRAF V600E mutation in PTC patients.…”

“…facilitates the determination of benign or malignant thyroid nodules that cannot be diagnosed by FNAB alone, effectively improving the accuracy of the clinical diagnosis of thyroid nodules (14). Many studies have found that PTC patients with the BRAF V600E mutation often have high disease invasiveness and poor prognosis, thus making it a valuable prognostic marker of the disease (13,(15)(16)(17)(18)(19).…”

BRAF V600E Mutation in Ameloblastoma: A Systematic Review and Meta-Analysis

“…Even though the status and exact mechanisms are still unclear, a high prevalence status may indicate a new treatment area exploration concerning this specific mutation. Previously, the BRAF V600E mutation focused on malignant tumours, where the prevalence was approximately 74.6% for papillary thyroid carcinoma [ 95 ], 7.4% for colorectal cancer [ 96 ], and 60% for melanomas [ 97 ]. According to previous studies, several gene mutations have been identified in the background of BRAF V600E positive mutation in ameloblastoma, including somatic mutation in cyclin-dependent kinase inhibitor 2A ( CDKN2A ), catenin beta 1 ( CTNNB1 ), fibroblast growth factor receptors ( FGFR ), Kirsten rat sarcoma virus ( KRAS ), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA ), and phosphatase and tensin homolog ( PTEN ) [ 19 , 98 ].…”

The Prognostic Significance of BRAF Gene Analysis in Children and Adolescents with Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis

“…Since there is a lack of definitive evidence on the clinicopathological significance of BRAF V600E in adult PTC, several meta-analyses have been conducted to elucidate its role in the diagnosis, management and prognosis of aggressive PTC cases. Various associations have been reported between the presence of BRAF V600E mutation and demographic data or risk factors, such as tumor size, multifocality, lymph node metastasis, vascular invasion, extra-thyroid extension, and advanced stage of tumor node metastasis [ 6 , 7 , 8 , 9 , 10 ].…”