AUTHOR=Censi Simona , Cavedon Elisabetta , Bertazza Loris , Galuppini Francesca , Watutantrige-Fernando Sara , De Lazzari Paola , Nacamulli Davide , Pennelli Gianmaria , Fassina Ambrogio , Iacobone Maurizio , Casal Ide Eric , Vianello Federica , Barollo Susi , Mian Caterina 

TITLE=Frequency and Significance of Ras, Tert Promoter, and Braf Mutations in Cytologically Indeterminate Thyroid Nodules: A Monocentric Case Series at a Tertiary-Level Endocrinology Unit

JOURNAL=Frontiers in Endocrinology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2017.00273

DOI=10.3389/fendo.2017.00273

ISSN=1664-2392

ABSTRACT=<sec id="ST1"><title>Purpose</title><p>The management of thyroid nodules of indeterminate cytology is controversial. Our study aimed to establish the frequency and significance of <italic>H-,K-,N-RAS, TERT</italic> promoter, and <italic>BRAF</italic> gene mutations in thyroid nodes of indeterminate cytology and to assess their potential usefulness in clinical practice.</p></sec><sec id="ST2"><title>Methods</title><p><italic>H</italic>-,<italic>K</italic>-,<italic>N-RAS, TERT</italic> promoter and <italic>BRAF</italic> gene mutations were examined in a series of 199 consecutive nodes of indeterminate cytology referred for surgical excision.</p></sec><sec id="ST3"><title>Results</title><p>69/199 (35%) were malignant on histopathological review. <italic>RAS</italic> mutations were detected in 36/199 (18%), and 19/36 cases (53%) were malignant on histological diagnosis. <italic>TERT</italic> promoter mutations were detected in 7/199 (4%) nodules, which were all malignant lesions. <italic>BRAF</italic> mutations were detected in 15/199 (8%), and a <italic>BRAF</italic> K601E mutation was identified in 2 follicular adenomas and 1 noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Altogether, this panel was able to identify 48% of the malignant lesions, achieving a specificity, positive predictive value, and negative predictive value for malignancy of 85, 62, and 75%, respectively.</p></sec><sec id="ST4"><title>Conclusion</title><p>The residual malignancy risk in mutation-negative nodes is 25%. These nodes still need to be resected, but mutation analysis could help to orient the appropriate surgical strategy.</p></sec>