Claire Bournaud1, Françoise Descotes2, Myriam Decaussin-Petrucci3, Julien Berthiller4, Christelle de la Fouchardière5, Anne-Laure Giraudet6, Mireille Bertholon-Gregoire7, Philip Robinson8, Jean-Christophe Lifante9, Jonathan Lopez10, Françoise Borson-Chazot11. 1. Hospices Civils de Lyon, Groupement Hospitalier Est, Service de Médecine Nucléaire, Bron Cedex, F-69677, France. Electronic address: claire.bournaud-salinas@chu-lyon.fr. 2. Hospices Civils de Lyon, Groupement Hospitalier Sud, Service de Biochimie et Biologie Moléculaire, Pierre Bénite, cedex, F-69495, France. 3. Hospices Civils de Lyon, Groupement Hospitalier Sud, Service D'Anatomie Pathologique, Pierre Bénite, cedex, F-69495, France; Université Lyon 1, Cancer Research Center of Lyon, INSERM1052 CNRS5286, Lyon, F-69008, France. 4. Hospices Civils de Lyon, Groupement Hospitalier Est, Service D'Epidémiologie Clinique, Pôle Information Médicale Evaluation Recherche, Bron Cedex, F-69677, France. 5. Centre Léon Bérard, Department of Medical Oncology, 28 Rue Laennec, Lyon, cedex, F-69373, France. 6. Centre Léon-Bérard, Dardre LaennecMedical Oncologyuat, 28, Rue Laennec, Lyon, cedex, F-69373, France. 7. Hospices Civils de Lyon, Groupement Hospitalier Est, Service de Médecine Nucléaire, Bron Cedex, F-69677, France. 8. Hospices Civils de Lyon, Direction de La Recherche Clinique et de L'Innovation, Lyon, cedex, F-69437, France. 9. Hospices Civils de Lyon, Groupement Hospitalier Sud, Service de Chirurgie Générale et Endocrinienne, Pierre Bénite, cedex, F-69495, France; Hospices Civils de Lyon, Fédération D'Endocrinologie, Bron Cedex, F-69677, France. 10. Hospices Civils de Lyon, Groupement Hospitalier Sud, Service de Biochimie et Biologie Moléculaire, Pierre Bénite, cedex, F-69495, France; Université Lyon 1, Cancer Research Center of Lyon, INSERM1052 CNRS5286, Lyon, F-69008, France. 11. Hospices Civils de Lyon, Fédération D'Endocrinologie, Bron Cedex, F-69677, France; Université Lyon 1, HESPER EA 7425, Lyon, F-69008, France.
Abstract
BACKGROUND: TERT promoter mutations are associated with adverse clinicopathological characteristics in thyroid carcinomas and considered as a major indicator of poor outcomes. Nevertheless, most studies have pooled heterogeneous types of thyroid carcinomas and have been conducted retrospectively. We investigated the association between TERT promoter mutations and recurrence in a prospective series of 173 intermediate- to high-risk patients with thyroid cancer. PATIENTS: Patients referred for radioiodine treatment after thyroidectomy for intermediate- to high-risk differentiated thyroid carcinoma were included in a prospective observational study and tested for TERT promoter, BRAF, and RAS mutations of their primary tumours. We analysed the relationship between TERT promoter mutations and outcomes. RESULTS: The prevalence of TERT promoter mutations was 20.2% (35/173) in the total population. It was significantly higher in tumours harbouring aggressive histological features (poorly differentiated carcinoma, tall cell variant of papillary cancer or widely invasive follicular cancer) than in non-aggressive tumours: 32.7% (16/49) versus 15.3% (19/124; p = 0.020). TERT promoter mutations were also strongly associated with age ≥45 years (p = 0.005), pT4 stage (p = 0.015), metastatic disease (p = 0.014), and extrathyroidal extension (p = 0.002). TERT promoter mutations were associated with poor outcomes in the total population (p < 0.001) but not in the subgroup of non-metastatic patients (p = 0.051). However, they were associated with a worse outcome in patients both free of metastases and devoid of aggressive histological features. Neither BRAF nor RAS mutations were associated with event-free survival in non-metastatic patients. CONCLUSION: Although their prognostic value does not seem to overcome that of histology, TERT promoter mutations may help to better define the prognosis of localized thyroid cancer patients without aggressive histology.
BACKGROUND:TERT promoter mutations are associated with adverse clinicopathological characteristics in thyroid carcinomas and considered as a major indicator of poor outcomes. Nevertheless, most studies have pooled heterogeneous types of thyroid carcinomas and have been conducted retrospectively. We investigated the association between TERT promoter mutations and recurrence in a prospective series of 173 intermediate- to high-risk patients with thyroid cancer. PATIENTS: Patients referred for radioiodine treatment after thyroidectomy for intermediate- to high-risk differentiated thyroid carcinoma were included in a prospective observational study and tested for TERT promoter, BRAF, and RAS mutations of their primary tumours. We analysed the relationship between TERT promoter mutations and outcomes. RESULTS: The prevalence of TERT promoter mutations was 20.2% (35/173) in the total population. It was significantly higher in tumours harbouring aggressive histological features (poorly differentiated carcinoma, tall cell variant of papillary cancer or widely invasive follicular cancer) than in non-aggressive tumours: 32.7% (16/49) versus 15.3% (19/124; p = 0.020). TERT promoter mutations were also strongly associated with age ≥45 years (p = 0.005), pT4 stage (p = 0.015), metastatic disease (p = 0.014), and extrathyroidal extension (p = 0.002). TERT promoter mutations were associated with poor outcomes in the total population (p < 0.001) but not in the subgroup of non-metastatic patients (p = 0.051). However, they were associated with a worse outcome in patients both free of metastases and devoid of aggressive histological features. Neither BRAF nor RAS mutations were associated with event-free survival in non-metastatic patients. CONCLUSION: Although their prognostic value does not seem to overcome that of histology, TERT promoter mutations may help to better define the prognosis of localized thyroid cancerpatients without aggressive histology.
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