The Correlation Between the Presence of BRAFV600E and TERT Promoter Mutation and the Response to Treatment with Iodine 131 in Differentiated Thyroid Cancer Patients.

Objectives: The response to radioiodine therapy (RAI) in differentiated thyroid cancer (DTC) patients is one of the most important factors that determines the treatment outcome and overall prognosis. The objective of this study is to determine the correlation between BRAFV600E and TERT promoter (TERTp) mutation in tumor samples of DTC patients with the response to RAI as well as correlation with clinical and pathohistological features. Methods: Samples of 110 DTC patients (80 with intermediate and high risk of disease recurrence-IHR and 30 with distant metastases) were analyzed for BRAFV600E and TERTp mutation (BRAF/TERT) and 89 patients were assessed for the response to RAI. Results: Sixty-one (55.5%) patients had BRAFV600E mutation, 30 (27.3%) had TERTp mutation, while 21 (19.1%) patients had both mutations. In the IHR group, the study showed a statistically significant association between genotype BRAF/TERTp and treatment outcome (p = 0.04). IHR DTC patients with BRAF-/TERT- finding showed in general an excellent response to RAI, while patients with BRAF/TERT co-mutation had a predominantly incomplete or indeterminate response. In DTC patients with BRAF/TERT co-mutation that presented with distant metastases, a tendency to a higher frequency of RAI-refractory (RAI-R) disease was recorded, but without statistical significance. The pathohistological and clinical features that significantly correlated with BRAF/TERT status are age at diagnosis, locoregional lymph node involvement, the largest positive lymph node diameter, tumor angioinvasion and the presence of distant metastases. Conclusions:BRAF/TERT co-mutation may be associated with a less favorable disease course and poorer response to RAI. However, findings in patients with distant metastases should be considered exploratory due to the limited sample size.