{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T08:32:35Z","timestamp":1774686755116,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,4,29]],"date-time":"2015-04-29T00:00:00Z","timestamp":1430265600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Molecular testing for genetic alterations associated with malignancy is a potential triage approach for thyroid fine\u2010needle aspiration (FNA) samples with indeterminate cytology. Because liquid\u2010based FNA material allows for efficient RNA extraction, the authors analyzed residual material for common point mutations and rearrangements.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Thyroid FNAs were classified according to The Bethesda System for Reporting Thyroid Cytopathology after routine ThinPrep slide preparation. Residual samples from malignant and indeterminate cases were submitted for molecular analysis, along with a random cohort of nondiagnostic and benign aspirates. Blinded analysis of <jats:italic>BRAF<\/jats:italic> and <jats:italic>RAS<\/jats:italic> point mutations and <jats:italic>RET\/PTC<\/jats:italic> and <jats:italic>PAX8\/PPAR\u03b3<\/jats:italic> rearrangements was correlated with subsequent follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Adequate results were obtained in 402 of 597 cases (67%). Mutations or rearrangements were detected in 24 of 117 cytologically indeterminate specimens (21%) (17 <jats:italic>RAS<\/jats:italic> rearrangements, 6 <jats:italic>BRAF<\/jats:italic> rearrangements, and 1 <jats:italic>PAX8\/PPAR\u03b3<\/jats:italic> rearrangement). <jats:italic>BRAF<\/jats:italic> mutations were preferentially associated with malignant cytologic diagnoses (22 of 42 cases; 52%), with less frequent detection in the suspicious for malignancy category (4 of 27 cases; 15%) and very low detection in all other categories (1%\u20104%). Surgical follow\u2010up confirmed malignancy in all 21 <jats:italic>BRAF<\/jats:italic>\u2010mutated cases, 42% of <jats:italic>RAS\u2010<\/jats:italic>mutated cases (10 of 24 cases), and 37% of cases with no detected mutation (39 of 105 cases).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Molecular analysis is feasible on residual ThinPrep material with the advantage of not requiring additional FNA procedures. The majority of <jats:italic>BRAF<\/jats:italic> mutations are identified in cases classified cytologically as malignant, and, to a lesser extent, as suspicious for malignancy. The usefulness of <jats:italic>BRAF<\/jats:italic> testing is limited by the low rate of <jats:italic>BRAF<\/jats:italic>\u2010positive cases in other categories, thereby highlighting the need to identify other genetic drivers of clinically aggressive thyroid cancers. <jats:bold><jats:italic>Cancer (Cancer Cytopathol)<\/jats:italic> 2015;123:356\u201361<\/jats:bold>. \u00a9 <jats:italic>2015 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.21546","type":"journal-article","created":{"date-parts":[[2015,4,29]],"date-time":"2015-04-29T15:54:03Z","timestamp":1430322843000},"page":"356-361","source":"Crossref","is-referenced-by-count":68,"title":["Molecular analysis of residual ThinPrep material from thyroid FNAs increases diagnostic sensitivity"],"prefix":"10.1002","volume":"123","author":[{"given":"Jeffrey F.","family":"Krane","sequence":"first","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital, Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edmund S.","family":"Cibas","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital, Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik K.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Medicine Brigham and Women's Hospital, Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Paschke","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Nephrology University of Leipzig Leipzig Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Eszlinger","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Nephrology University of Leipzig Leipzig Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,4,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-87666-5"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-1469"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29038"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1203208"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2013.0278"},{"key":"e_1_2_7_7_1","first-page":"476","article-title":"Fine\u2010needle aspiration cytology of thyroid nodules: molecular diagnostics in a routine diagnostic setting [in German]","volume":"139","author":"Eszlinger M","year":"2014","journal-title":"Dtsch Med Wochenschr"},{"key":"e_1_2_7_8_1","article-title":"Molecular testing of thyroid fine\u2010needle aspirations improves presurgical diagnosis and supports the histological identification of minimally invasive follicular thyroid carcinomas [published online ahead of print January 28, 2015]","author":"Eszlinger 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