Endocr Pract. 2021 Dec 7:S1530-891X(21)01410-5. doi: 10.1016/j.eprac.2021.12.005. Online ahead of print.
ABSTRACT
OBJECTIVE: To assess the impact of BRAFV600E and telomerase reverse transcriptase (TERT) promoter mutations in distant-metastatic differentiated thyroid cancer (DM-DTC) patients based on thyroglobulin (Tg) response to radioactive iodine (RAI) therapy.
METHODS: BRAFV600E and TERT mutations in primary tumors or metastatic lymph nodes of 114 DM-D TC patients were retrospectively examined. RAI avidity was evaluated based on posttreatment 131I-WBS. Tg response was dynamically assessed with a median follow-up of 56.50 months (interquartile range, 28.43-97.98 months).
RESULTS: BRAFV600E was detected in 38.6% of cases and TERT mutation in 21.1% of cases, and both BRAFV600E and TERT mutations were observed in 14.9% of cases. Patients with both mutations tended to be older at diagnosis (P<0.001), less multifocal (P=0.011) and have more aggressive histologic subtypes (P=0.011) and a higher Ki-67 index (P=0.003). Patients with neither mutation tended to be more RAI-avid than those with the BRAFV600E mutant alone or both mutations (P=0.001, <0.001, respectively). Patients with both mutations presented more unfavorable Tg response than those without both mutations and with the BRAFV600E mutant alone (P=0.001, 0.013, respectively). Tg progression-free survival (Tg-PFS) w as shorter in patients with TERT mutation alone than in those with neither mutation (P=0.021), and it tended to be shorter when BRAFV600E coexisted (P<0.001); however, no significant difference was observed between BRAFV600E alone and neither mutation (P=0.890).
CONCLUSIONS: Coexistence of BRAFV600E and TERT promoter mutations synergistically induce loss of RAI avidity and an undesirable Tg response in DM-DTC. TERT promoter mutation appears to affect Tg response more than the BRAFV600E mutation.
PMID:34890787 | DOI:10.1016/j.eprac.2021.12.005
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