Giulia Brigante1,2, Andrea Craparo3,4, Elisa Pignatti3, Marco Marino3, Maria Laura Monzani3,4, Sara De Vincentis3,4, Livio Casarini3,5, Samantha Sperduti3,5, Gisella Boselli3,4, Gianluca Margiotta3,4, Margherita Ippolito3, Vincenzo Rochira3,4, Manuela Simoni3,4. 1. Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy. giulia.brigante@unimore.it. 2. Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy. giulia.brigante@unimore.it. 3. Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy. 4. Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Modena, Italy. 5. Center for Genomic Research, University of Modena and Reggio Emilia, Modena, Italy.
Abstract
PURPOSE: This study aimed to evaluate the real-life use of BRAF-V600E mutation analysis in washout liquid from thyroid nodule fine needle aspiration (FNA), and the consequences of genetic result on clinical decision-making. METHODS: We retrospectively considered subjects tested for BRAF-V600E among those attending the Endocrinology Unit of Modena for FNA between 2014 and 2018. Washing fluid was collected together with cytological sample and stored at -20 °C. If the clinician deemed it necessary, the sample was thawed, DNA extracted, and genetic test performed by high-resolution melting technique. We collected data on cytology according to the Italian Consensus for the cytological classification of thyroid nodules, type of surgery (when performed), histology, and adverse events. RESULTS: Out of 7112 subjects submitted to FNA, BRAF analysis was requested for 683 (9.6%). Overall, 896 nodules were analyzed: 74% were indeterminate at cytology, mainly TIR3A (low risk). Twenty-two nodules were mutant (BRAF+). Only 2% of indeterminate, mainly TIR3B, were BRAF+. Based on final histological diagnosis, BRAF test had high specificity (100%) but poor sensitivity (21%), also in indeterminate nodules. Mutant subjects underwent more extensive surgery compared to wild type (p = 0.000), with frequent prophylactic central lymph node dissection. One third had local metastases. Higher prevalence of hypoparathyroidism was found in BRAF+ compared to wild type (p = 0.018). CONCLUSIONS: The analysis of BRAF-V600E outside of gene panels has low sensitivity, especially in indeterminate nodules, and a positive result could lead to more extensive surgery with greater risk of hypoparathyroidism and questionable clinical utility.
PURPOSE: This study aimed to evaluate the real-life use of BRAF-V600E mutation analysis in washout liquid from thyroid nodule fine needle aspiration (FNA), and the consequences of genetic result on clinical decision-making. METHODS: We retrospectively considered subjects tested for BRAF-V600E among those attending the Endocrinology Unit of Modena for FNA between 2014 and 2018. Washing fluid was collected together with cytological sample and stored at -20 °C. If the clinician deemed it necessary, the sample was thawed, DNA extracted, and genetic test performed by high-resolution melting technique. We collected data on cytology according to the Italian Consensus for the cytological classification of thyroid nodules, type of surgery (when performed), histology, and adverse events. RESULTS: Out of 7112 subjects submitted to FNA, BRAF analysis was requested for 683 (9.6%). Overall, 896 nodules were analyzed: 74% were indeterminate at cytology, mainly TIR3A (low risk). Twenty-two nodules were mutant (BRAF+). Only 2% of indeterminate, mainly TIR3B, were BRAF+. Based on final histological diagnosis, BRAF test had high specificity (100%) but poor sensitivity (21%), also in indeterminate nodules. Mutant subjects underwent more extensive surgery compared to wild type (p = 0.000), with frequent prophylactic central lymph node dissection. One third had local metastases. Higher prevalence of hypoparathyroidism was found in BRAF+ compared to wild type (p = 0.018). CONCLUSIONS: The analysis of BRAF-V600E outside of gene panels has low sensitivity, especially in indeterminate nodules, and a positive result could lead to more extensive surgery with greater risk of hypoparathyroidism and questionable clinical utility.
Authors: Elizabeth J de Koster; Lioe-Fee de Geus-Oei; Olaf M Dekkers; Ilse van Engen-van Grunsven; Jaap Hamming; Eleonora P M Corssmit; Hans Morreau; Abbey Schepers; Jan Smit; Wim J G Oyen; Dennis Vriens Journal: Endocr Rev Date: 2018-04-01 Impact factor: 19.871
Authors: Richard T Kloos; Jessica D Reynolds; P Sean Walsh; Jonathan I Wilde; Edward Y Tom; Moraima Pagan; Catalin Barbacioru; Darya I Chudova; Mei Wong; Lyssa Friedman; Virginia A LiVolsi; Juan Rosai; Richard B Lanman; Giulia C Kennedy Journal: J Clin Endocrinol Metab Date: 2013-03-08 Impact factor: 5.958
Authors: Salvatore Vaccarella; Silvia Franceschi; Freddie Bray; Christopher P Wild; Martyn Plummer; Luigino Dal Maso Journal: N Engl J Med Date: 2016-08-18 Impact factor: 91.245
Authors: N Paul Ohori; Jenna Wolfe; Steven P Hodak; Shane O LeBeau; Linwah Yip; Sally E Carty; Umamaheswar Duvvuri; Karen E Schoedel; Marina N Nikiforova; Yuri E Nikiforov Journal: Cancer Cytopathol Date: 2013-07-23 Impact factor: 5.284
Authors: Cosimo Durante; Giorgio Grani; Livia Lamartina; Sebastiano Filetti; Susan J Mandel; David S Cooper Journal: JAMA Date: 2018-03-06 Impact factor: 56.272