Effect of BRAFV600E and TERT Promoter Mutations on Thyroglobulin Response in Patients with Distant-Metastatic Differentiated Thyroid Cancer.

Objective: To assess the impact of serine/threonine-protein kinase B-Raf (BRAF) V600E and telomerase reverse transcriptase (TERT) promoter mutations in patients with distant-metastatic differentiated thyroid cancer (DM-DTC) based on thyroglobulin (Tg) response to radioactive iodine (RAI) therapy. Methods: The BRAF(V600E) and TERT mutations in primary tumors or metastatic lymph nodes of 114 patients with DM-DTC were retrospectively examined. RAI avidity was evaluated using a posttreatment iodine-131 whole-body scan. The Tg response was dynamically assessed at a median follow-up period of 56.50 months (interquartile range, 28.43-97.98 months). Results: BRAF(V600E) was detected in 38.6% of cases, the TERT mutation in 21.1% of cases, and both the BRAF(V600E) and TERT mutations in 14.9% of cases. Patients with both the mutations tended to be older at diagnosis (P <.001) and less multifocal (P = .011) and have more aggressive histologic subtypes (P = .011) and a higher Ki-67 index (P = .003). Patients with neither mutation tended to be have more RAI avidity than those with either the BRAF(V600E) mutation alone or both the mutations (P = .001 and .001, respectively). Patients with both the mutations exhibited a more unfavorable Tg response than those without both the mutations and those with the BRAF(V600E) mutation alone (P = .001 and .013, respectively). The Tg progression-free survival was shorter in patients with the TERT mutation alone than in those with neither mutation (P = .021), and it tended to be shorter when it coexisted with the BRAF(V600E) mutation (P <.001); however, no significant difference was observed between those with the BRAF(V600E) mutation alone and those with neither mutation (P = .890). Conclusion: The coexistence of the BRAF(V600E) and TERT promoter mutations synergistically induce the loss of RAI avidity and leads to an undesirable Tg response in patients with DM-DTC. The TERT promoter mutation appears to affect Tg response more than the BRAF(V600E) mutation. (c) 2021 AACE. Published by Elsevier Inc. All rights reserved.