ECE2019 Guided Posters Thyroid Nodules and Cancer (12 abstracts)
Prognostic significance of TERT promoter and BRAF mutations in cytologically suspicious or malignant thyroid nodules: a monocentric case series at a tertiary-level endocrinology unit
Simona Censi 1 , Susi Barollo 1 , Elisabetta Grespan 1 , Sara Watutantrige-Fernando 1 , Elisabetta Cavedon 1 , Jacopo Manso 1 , Maurizio Iacobone 2 , Eric Casal Ide 2 , Francesca Galuppini 3 , Ambrogio Fassina 3 , Gianmaria Pennelli 3 , Federica Vianello 4 , Loris Bertazza 1 & Caterina Mian 1
1Department of Medicine (DIMED), Endocrinology Unit; University of Padova, Padova, Italy; 2Endocrine Surgery Unit, Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padova, Padova, Italy; 3Surgical Pathology and Cytopathology Unit, Pathology Unit, Department of Medicine (DIMED), University of Padova, Padova, Italy; 4Department of Radiotherapy, Istituto Oncologico Veneto-IRCCS, Padova, Italy.
Background: Follicular-derived thyroid cancers (FDTC) generally have a good prognosis. Nonetheless, a minority of them have an aggressive behavior and develop distant metastases, with increased mortality rates. Pre-surgically available prognostic markers, able to identify this group of patients are still lacking.
Materials and methods: The study involved 436 FNA samples with a malignant/suspicious cytology obtained from thyroid nodules in 436 consecutive patients referred for surgical excision from April 2007 to January 2017. Molecular analysis for somatic mutations of TERT promoter was retrospectively performed in all patients. 434 patients also underwent BRAF analysis. 131I remnant ablation was performed in 387 patients (median dose: 100 mCi; range: 30–200 mCi). Follow-up was available for 384 patients (median: 59 months, range: 7-293 months).
Results: TERT promoter mutations and BRAF mutations were detected in 20/436 (4.6%) and in 257/434 thyroid nodules (59.2%), respectively. At the end of the follow-up, 319/384 patients (83%) had an excellent outcome, 37/384 (9.7%) had an indeterminate response and 28/384 (7.3%) had biochemical or structural persistent disease or died because of disease progression. Tumor size (P=0.002), presence of extrathyroidal extension (P=0.0015), vascular invasion (P=0.0024), lymph node involvement (P=0.0001), mostly N1b spread (P<0.0001), distant metastasis (DM) (P<0.0001), advanced stage at diagnosis (P<0.0001) and TERT promoter mutation (P=0.0002) were all significantly correlated with the risk of persistent/recurrent disease or disease-related death. At multivariate analysis, only cancer size (OR 1.06, 95% CI 1.01 to 1.09), the presence of N1b lymph-node metastases (OR 8.09, 95% CI 2.62 to 25.04) and DM (OR 7.32, 95% CI 1.17 to 45.81) predicted persistence disease or cancer-related death. TERT promoter mutations were related with older age (P<0.0001), largest tumor size (P=0.0002), higher tumor stages (P<0.0001), and DM (P<0.0001). DM was correlated with older age (P=0.0487), larger tumor size (P=0.0015), extra-thyroidal extension (P=0.0120), presence of N1b (P=0.0001) and TERT promoter mutation (P<0.0001). Presence of BRAF mutation was less frequent in patients with DM (P=0.0201). TERT promoter mutations (OR 40.58; 95% CI 3.06 to 539.04) and N1b (OR 40.16, 95% CI 3.48 to 463.04) were independent predictors of DM at multivariate analysis.
Conclusions: TERT promoter mutation was an independent predictor for DM, giving the clinician the possibility to individuate, already in the pre-surgical setting, many of the patients who deserve a more aggressive initial treatment and a closer follow-up.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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