Frequency and Clinical Impact of BRAF and RAS Mutations in Follicular Variant Papillary Thyroid Carcinoma

Background and aims: Inconsistent findings have been reported regarding the frequency and clinical impact of BRAF and RAS mutations in Follicular Variant Papillary Thyroid Carcinoma (FVPTC). Materials and methods: We systematically searched the PubMed and Embase libraries and The Cancer Genome Atlas Program (TCGA) and The International Cancer Genome Consortium (ICGC) databases. One part focused on the frequency distribution of BRAF and RAS gene mutations in FVPTC and its various histological subtypes, while another explored their clinical associations. Results: Our meta-analysis comprised a large sample size of 10,902 FVPTC patients, including 2,370 cases with relevant mutation-related clinical information. The overall mutation rates for BRAF and RAS in FVPTC were found to be 19.9% and 35.3%, with the highest incidence of BRAF (31.0%) and RAS (37.5%) mutations observed in invasive FVPTC and non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), respectively. No significant gender or age differences were documented between patients with mutated versus wild-type FVPTCs. In comparison to wild-type patients, those with BRAF mutations were significantly associated with tumor multifocality (OR 1.65; 95% CI, 1.21-2.25; PRAS mutations. Conclusion: As highlighted by our meta-analysis, RAS mutations were found to be more prevalent in FVPTC than BRAF mutations. Interestingly, while the frequency of BRAF mutations was higher in invasive subtypes, benign exhibited the opposite trend with RAS mutations being more commonly identified. Furthermore, we also noted that FVPTC patients with BRAF mutations had a higher risk of poor clinical outcomes, while RAS mutations did not show similar associations. Keywords: Follicular Variant Papillary Thyroid Carcinoma, BRAF, RAS, Frequency, Histology, Clinical feature, Meta-Analysis