TERT Promoter Mutations Are a Major Indicator of Poor Outcome in Differentiated Thyroid Carcinomas

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Miguel Melo (Author) Other; Adriana Gaspar da Rocha (Author) Other; Joao Vinagre (Author) Other; Rui Batista (Author) Other; Joana Peixoto (Author) Other; Catarina Tavares (Author) Other; Ricardo Celestino (Author) Other; Ana Almeida (Author) Other; Catarina Salgado (Author) Other; Catarina Eloy (Author) Other; Patricia Castro (Author) Other; Hugo Prazeres (Author) Other; Jorge Lima (Author) FMUP; Teresina Amaro (Author) Other; Claudia Lobo (Author) Other; Maria Joao Martins (Author) Other; Margarida Moura (Author) Other; Branca Cavaco (Author) Other; Valeriano Leite (Author) Other; Jose Manuel Cameselle Teijeiro (Author) Other; Francisco Carrilho (Author) Other; Manuela Carvalheiro (Author) Other; Valdemar Maximo (Author) Other; Manuel Sobrinho Simoes (Author) Other; Paula Soares (Author) FMUP

Journal

Title: Journal of Clinical Endocrinology and Metabolism

Vol. 99

Pages: E754-E765

ISSN: 0021-972X

Publisher: Endocrine Society

Indexing

ISI Web of Knowledge - 392 Citations

Scopus - 430 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-009-DWN

DOI: 10.1210/jc.2013-3734

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12