Endocrine Abstracts

Introduction: Coexistence of the BRAF V600E and TERT promoter mutations may correlate with more aggressive histopathological features and worse course of the disease. According to the American Thyroid Association (ATA) dynamic risk stratification with modified initial estimated risk based on response- to-therapy and disease course allows individual risk assessment and support clinicians in the appropriate management approach to differentiated thyroid cancer (DTC).

Aim: The aim of this study was to examine the relation between the coexistence of the BRAF V600E and TERT promoter mutations in the papillary thyroid cancer (PTC) and response to therapy according to the ATA guidelines.

Participants: Unselected 568 PTC cases with known BRAF and TERT status diagnosed from 2000–2012 and actively monitored at one institution were reviewed retrospectively.

Main outcome measures: The association between the BRAF V600E and TERT promoter mutation and clinicopathological features, TNM stages, initial risk, response-to-therapy categories, follow-up, and the final outcome of the disease according to the revised 2015 ATA criteria and the 8th edition of the American Joint Committee on Cancer/Tumor-Node-Metastasis (AJCC/TNM) staging system.

Results: Any TERT promoter (TERTp) mutations were detected in 13.5% (77/568) of PTC cases with known BRAF status. The C228T and C250T mutations were 54 (9.5%) and 23 (4%) patients, respectively. Twenty-two additional other TERT alterations were found. Coexistence BRAF V600E and TERT hotspot C228T or C250T promoter mutation was found in 9.5% (54/568). Concurrent BRAF and TERTp positive status correlated significantly with older patient’s age (P=0.001), gross extrathyroidal extension (P=0.003), pT3–4 tumor stage (P=0.005), stage II-IV according to the AJCC/TNM (P=0.019), and ATA intermediate or high risk according to the 2015 ATA initial risk stratification (P=0.003), as well as with the worse than excellent category of response to primary therapy (P=0.045), recurrence (P=0.015) and no remission in the final outcome (P=0.014). During a median follow-up of 120 months (10 years), 16 (29.6%) patients BRAF (+) and TERT (+) did not achieve excellent response to primary therapy, three (5.6%) were recurrent after a disease-free period and eight (14.8%) presented no remission at the end of follow-up.

Conclusions: The positive BRAF V600E and TERT mutation in patients with PTC correlate with poor prognostic initial factors and clinical course. Coexistence the BRAF and TERT status seems to be suitable for predicting a worse response-to-therapy, recurrence, and poor outcome.