Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.22/5395
Título: TERT Promoter Mutations Are a Major Indicator of Poor Outcome in Differentiated Thyroid Carcinomas
Autor: Melo, Miguel
Rocha, Adriana Gaspar
Vinagre, João
Batista, Rui
Peixoto, Joana
Tavares, Catarina
Celestino, Ricardo
Almeida, Ana
Salgado, Catarina
Eloy, Catarina
Castro, Patrícia
Prazeres, Hugo
Lima, Jorge
Amaro, Teresina
Lobo, Cláudia
Martins, Maria João
Moura, Margarida
Cavaco, Branca
Leite, Valeriano
Cameselle-Teijeiro, José
Carrilho, Francisco
Carvalheiro, Manuela
Máximo, Valdemar
Sobrinho-Simões, Manuel
Soares, Paula
Data: Mai-2014
Editora: R. Paul Robertson
Resumo: 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.
Peer review: yes
URI: http://hdl.handle.net/10400.22/5395
DOI: 10.1210/jc.2013-3734
Versão do Editor: http://press.endocrine.org/doi/full/10.1210/jc.2013-3734
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