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Endocrine Abstracts (2014) 35 P1149 | DOI: 10.1530/endoabs.35.P1149

1Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; 2Department of Endocrinology, Diabetes and Metabolism, Center of Coimbra, University and Hospital, Coimbra, Portugal; 3Medical Faculty, University of Porto, Porto, Portugal; 4Institute of Biomedical Sciences of Abel Salazar, University of Porto, Porto, Portugal; 5Department of Pathology and Oncology, Medical Faculty, University of Po, Porto, Portugal; 6Department of Pathology, Hospital Pedro Hispano, Matosinhos, Portugal; 7Department of Pathology, Portuguese Institute of Oncology – Porto Center, Porto, Portugal; 8Portuguese Institute of Oncology – Lisbon Center, Center for Investigation of Molecular Pathobiology, Lisboa, Portugal; 9Faculty of Medical Sciences, Center for the Study of Chronic Diseases, University of Lisbon, Lisboa, Portugal; 10Department of Endocrinology, Portuguese Institute of Oncology – Lisbon Center, Lisboa, Portugal; 11Department of Pathology, Medical Faculty, Clinical University Hospital, SERGAS, University of Santiago de Compostela, Santiago de Compostela, Spain; 12Department of Pathology, Hospital S João, Porto, Portugal.


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 (DTC).

Material and Methods: We studied 647 tumours and tumour-like lesions. A total of 469 patients with FCDTC treated and followed in five University Hospitals were included. Mean follow-up (±S.D.) was 7.8±5.8 years. We evaluate the predictive value of TERT promoter mutations and other clinico-pathological and molecular features (BRAF, NRAS) 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 (PTC), 17.1% of follicular carcinomas (FTC), 29.0% of poorly differentiated carcinomas and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumours were older (P<0.001) and had larger tumours (P=0.002). In DTC, TERT promoter mutations were significantly associated with distant metastases (P<0.001) and higher stage (P<0.001). Patients with DTC harbouring TERT promoter mutations were submitted to more radioiodine treatments (P=0.009) with higher cumulative dose (p=0.004), and to more treatment modalities (P=0.001). At the end of follow-up, patients with TERT-mutated DTC were more prone to have persistent disease (P=0.001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P<0.001)] in DTC (P<0.001), in PTC (P=0.001) and in FTC (P<0.001). After adjusting for age at diagnosis and gender, the HR was 10.35 (95%CI 2.01–53.24; P=0.005) in DTC and 23.81 (95%CI 1.36–415.76; P=0.03) in PTC.

Conclusions: TERT promoter mutations are an indicator of clinically aggressive tumours, 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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