TERT Promoter and BRAF V600E Mutations in Papillary Thyroid Cancer: A Single-Institution Experience in Korea

Simple Summary TERT promoter mutation has recently emerged as a promising prognostic biomarker for aggressive papillary thyroid cancer (PTC), along with BRAF B600E mutation. The prevalence of the TERT promoter mutations has been reported as relatively uncommon in Asian countries. We report on a prospective study of the TERT promoter and BRAF V600E mutation in the largest number of subjects with PTC in Korea. We assume that our specific clinical settings and the favorable healthcare environment in Korea led to several distinct findings: the lowest prevalence of TERT promoter mutation ever reported, multifocal gene mutations in bilateral PTCs, and more early-stage papillary microcarcinomas included in this study. This study indicates that relevant evaluation and treatment strategies should be investigated continuously based on different circumstances. Telomerase reverse transcriptase (TERT) promoter mutation has been investigated for its clinical and prognostic significance in aggressive papillary thyroid cancer (PTC). In this study, we aimed to assess the prevalence, clinicopathologic features, and treatment outcomes of TERT mutation-positive PTCs along with the common BRAF V600E mutation. We performed mutational analyses for BRAF and the TERT promoter in thyroid cancer patients who had undergone surgery at our institution since 2019. We reviewed and analyzed 7797 patients with PTC in this study. The prevalence of BRAF V600E and TERT promoter mutations was 84.0% and 1.1%, respectively. Multifocal gene mutations in bilateral PTCs were identified. TERT promoter mutations were associated with older age, larger tumor size, tumor multifocality, tumor variants, advanced stages, more adjuvant radioactive iodine treatment (RAI), higher stimulated serum thyroglobulin level before RAI, and more uptakes in the regions outside the surgical field on a post-RAI whole-body scan. The coexistence of BRAF V600E and TERT promoter mutations exacerbated all clinicopathologic characteristics. The frequency of TERT promoter mutations was the lowest in this study, compared to previous studies. TERT promoter mutations consistently correlated with aggressive PTCs, and the synergistic effect of both mutations was evident. Specific clinical settings in our institution and in Korea may have led to these distinctive results. Prospective multicenter studies with longer follow-up periods are required to establish valuable oncologic outcomes.

Automated summary

TERT promoter mutation, investigated for its clinical and prognostic significance in aggressive PTC, showed the lowest prevalence in Korea among a large cohort of PTC patients. The presence of TERT promoter mutations consistently correlated with aggressive PTCs, with a synergistic effect when coexisting with BRAF V600E mutation. Further prospective multicenter studies are needed to establish valuable oncologic outcomes.