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Journal of Clinical Endocrinology and MetabolismVolume 99, Issue 5, May 2014, Pages E754-E765

TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas(Article)(Open Access)

  • Melo, M.,
  • Da Rocha, A.G.,
  • Vinagre, J.,
  • Batista, R.,
  • Peixoto, J.,
  • Tavares, C.,
  • Celestino, R.,
  • Almeida, A.,
  • Salgado, C.,
  • Eloy, C.,
  • Castro, P.,
  • Prazeres, H.,
  • Lima, J.,
  • Amaro, T.,
  • Lobo, C.,
  • Martins, M.J.,
  • Moura, M.,
  • Cavaco, B.,
  • Leite, V.,
  • Cameselle-Teijeiro, J.M.,
  • Carrilho, F.,
  • Carvalheiro, M.,
  • Máximo, V.,
  • Sobrinho-Simões, M.,
  • Soares, P.
  • View Correspondence (jump link)
  • aInstitute of Molecular Pathology and Immunology, University of Porto, Rua Dr Roberto Frias s/n, 4200-465 Porto, Portugal
  • bMedical Faculty, University of Porto, 4200-139 Porto, Portugal
  • cInstitute of Biomedical Sciences of Abel Salazar, University of Porto, 4050-313 Porto, Portugal
  • dDepartment of Pathology and Oncology, Medical Faculty, University of Porto, 4200-139 Porto, Portugal
  • eDepartments of Endocrinology, Diabetes, and Metabolism and Pathology, University and Hospital Center of Coimbra, 3000-075 Coimbra, Portugal
  • fUnit of Endocrinology, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
  • gSchool of Allied Health Sciences, ESTSP - Escola Superior de Tecnologia da Saúde Do Porto, Polytechnic of Porto, 4400-330 Vila Nova de Gaia, Portugal
  • hPortuguese Institute of Oncology, Coimbra Center, 3000-075 Coimbra, Portugal
  • iDepartment of Pathology, Hospital Pedro Hispano, 4464-513 Matosinhos, Portugal
  • jDepartment of Pathology, Portuguese Institute of Oncology, Porto Center, 4200-072 Porto, Portugal
  • kCenter for Investigation of Molecular Pathobiology, Department of Endocrinology, Portuguese Institute of Oncology, 1099-023 Lisbon, Portugal
  • lCenter for the Study of Chronic Diseases, Faculty of Medical Sciences, University of Lisbon, 1099-085 Lisbon, Portugal
  • mDepartment of Pathology, Clinical University Hospital, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
  • nDepartment of Pathology, Hospital S. João, 4200-319 Porto, Portugal

Abstract

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:Weaimed 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. © 2014 by the Endocrine Society.

Indexed keywords

EMTREE drug terms:radioactive iodinetelomerase
EMTREE medical terms:adultanaplastic thyroid cancerarticlecancer mortalitycancer prognosiscancer stagingcontrolled studydifferentiated thyroid cancerdistant metastasisfemalefollow upgene mutationhumanhuman tissuemajor clinical studymaleobservational studypredictive valuepriority journalpromoter regionretrospective studytelomerase genethyroid follicular carcinomathyroid papillary carcinoma
MeSH:Adenocarcinoma, FollicularAdultAgedCarcinoma, PapillaryFemaleHumansMaleMiddle AgedMutationPrognosisPromoter Regions, GeneticRetrospective StudiesTelomeraseThyroid Neoplasms
  • ISSN: 0021972X
  • CODEN: JCEMA
  • Source Type: Journal
  • Original language: English
  • DOI: 10.1210/jc.2013-3734
  • PubMed ID: 24476079
  • Document Type: Article
  • Publisher: Endocrine Society

  Soares, P.; Institute of Molecular Pathology and Immunology, University of Porto, Rua Dr Roberto Frias s/n, Portugal;
© Copyright 2014 Elsevier B.V., All rights reserved.

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