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JOURNAL ARTICLE

TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas

Miguel Melo, Adriana Gaspar da Rocha, João Vinagre, Rui Batista, Joana Peixoto, Catarina Tavares, Ricardo Celestino, Ana Almeida, Catarina Salgado, Catarina Eloy, Patrícia Castro, Hugo Prazeres, Jorge Lima, Teresina Amaro, Cláudia Lobo, Maria João Martins, Margarida Moura, Branca Cavaco, Valeriano Leite, José Manuel Cameselle-Teijeiro, Francisco Carrilho, Manuela Carvalheiro, Valdemar Máximo, Manuel Sobrinho-Simões, Paula Soares
Journal of Clinical Endocrinology and Metabolism 2014, 99 (5): E754-65
24476079

CONTEXT: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers.

OBJECTIVES: We aimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs).

DESIGN: This was a retrospective observational study.

SETTING AND PATIENTS: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years.

MAIN OUTCOME MEASURES: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality.

RESULTS: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P < .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P = .001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P = .001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01-53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36-415.76; P = .03) in PTCs.

CONCLUSIONS: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC.

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