TERT promoter mutations and long-term survival in patients with thyroid cancer

<jats:p><jats:italic>TERT</jats:italic> promoter mutations are emerging prognostic biomarkers in multiple cancers and are found in highly aggressive thyroid cancer. Our aim is to investigate the prognostic value of these mutations for the outcome of thyroid cancer-related mortality in a large cohort of thyroid cancer patients. This was a retrospective study of 409 patients (393 with differentiated thyroid cancer) with a median age of 44 years (range 16–81 years) and median follow-up of 13 years (interquartile range 11–16 years). Analyses of associations between mutational status and various clinicopathological variables were performed. <jats:italic>TERT</jats:italic> promoter mutations were identified in 32 (9.8%) papillary, 11 (16.7%) follicular and seven (43.8%) poorly differentiated/anaplastic thyroid cancer patients. The presence of <jats:italic>TERT</jats:italic> promoter mutations was associated with factors such as increased age (<jats:italic>P</jats:italic> < 0.001), extrathyroidal invasion (<jats:italic>P</jats:italic> = 0.01), increased stage at diagnosis (<jats:italic>P</jats:italic> < 0.001) and dedifferentiated histological type (<jats:italic>P</jats:italic> = 0.001). A <jats:italic>TERT</jats:italic> promoter mutation was independently associated with poorer overall survival in patients with differentiated thyroid cancer (10-year survival rate, 66.2% vs 98.3% for wild type; adjusted HR, 7.18; 95% CI: 2.77–18.59) and in patients with papillary cancer (74.2% vs 99.3%; 14.20; 3.03–66.68). Concomitant <jats:italic>TERT</jats:italic> and <jats:italic>BRAF</jats:italic> mutations worsened the survival rate of patients with papillary cancer (82.6% vs 99.4% for exclusively <jats:italic>BRAF</jats:italic> mutation alone; 5.62; 1.85–17.09). In conclusion, the presence of <jats:italic>TERT</jats:italic> promoter mutations is independently associated with increased mortality in patients with differentiated thyroid cancer. The results suggest that inclusion of <jats:italic>TERT</jats:italic> promoter mutation analysis with conventional clinicopathological evaluation can lead to better prognostication and management for individual patients.</jats:p>