{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T20:53:21Z","timestamp":1768424001060,"version":"3.49.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,2,2]],"date-time":"2017-02-02T00:00:00Z","timestamp":1485993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Thyroid nodules with atypia of undetermined significance (AUS) on fine\u2010needle aspiration (FNA) have a low risk of malignancy that appears to vary based on specific features described in the AUS diagnosis. The Afirma gene expression classifier (GEC) is a molecular test designed to improve preoperative risk stratification of thyroid nodules, but its performance for different patterns of AUS has not been defined. The objective of this study was to assess GEC results and clinical outcomes in AUS nodules with architectural atypia (AUS\u2010A), cytologic atypia (AUS\u2010C) or both (AUS\u2010C\/A).<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>This was a retrospective review of all thyroid nodules with AUS cytopathology that underwent GEC testing at the authors' institution over a period of &gt;4 years.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>In 227 nodules that had AUS cytology results and Afirma GEC testing, the rate of benign GEC results was higher in AUS\u2010A nodules (70 of 107; 65%) than in AUS\u2010C\/A nodules (25 of 65; 38%; <jats:italic>P<\/jats:italic>\u2009=\u2009.0008), and AUS\u2010C nodules exhibited an intermediate rate of benign results (27 of 55 nodules; 59%). The risk of cancer among patients who had GEC\u2010suspicious nodules, 86% of whom underwent resection, was 19% (6 of 25) for AUS\u2010A nodules compared with 57% (21 of 37) for AUS\u2010C\/A nodules (<jats:italic>P<\/jats:italic>\u2009=\u2009.003) and 45% (10 of 22) for AUS\u2010C nodules (<jats:italic>P<\/jats:italic>\u2009=\u2009.07). In nodules that had an indeterminate repeat cytology result, no difference was observed in the rate of benign GEC results or in the malignancy rate compared with nodules that had a single cytology result.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The performance characteristics of Afirma GEC testing vary, depending on qualifiers of cytologic atypia. Recognition of these differences may enable clinicians to provide improved counseling and treatment recommendations to patients. <jats:bold><jats:italic>Cancer Cytopathol<\/jats:italic> 2017;125:313\u2013322.<\/jats:bold> \u00a9 <jats:italic>2017 American Cancer Society.<\/jats:italic><\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.21827","type":"journal-article","created":{"date-parts":[[2017,2,2]],"date-time":"2017-02-02T14:20:38Z","timestamp":1486045238000},"page":"313-322","source":"Crossref","is-referenced-by-count":68,"title":["Qualifiers of atypia in the cytologic diagnosis of thyroid nodules are associated with different Afirma gene expression classifier results and clinical outcomes"],"prefix":"10.1002","volume":"125","author":[{"given":"Sylvan C.","family":"Baca","sequence":"first","affiliation":[{"name":"Department of Medicine The Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristine S.","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Pathology The Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyle C.","family":"Strickland","sequence":"additional","affiliation":[{"name":"Department of Pathology The Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard T.","family":"Heller","sequence":"additional","affiliation":[{"name":"Department of Radiology The Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew I.","family":"Kim","sequence":"additional","affiliation":[{"name":"Thyroid Section, Division of Endocrinology, Hypertension, and Diabetes, The Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justine A.","family":"Barletta","sequence":"additional","affiliation":[{"name":"Department of Pathology The Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1987-2004","authenticated-orcid":false,"given":"Edmund S.","family":"Cibas","sequence":"additional","affiliation":[{"name":"Department of Pathology The Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7768-3901","authenticated-orcid":false,"given":"Jeffrey F.","family":"Krane","sequence":"additional","affiliation":[{"name":"Department of Pathology The Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen","family":"Marqusee","sequence":"additional","affiliation":[{"name":"Thyroid Section, Division of Endocrinology, Hypertension, and Diabetes, The Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trevor E.","family":"Angell","sequence":"additional","affiliation":[{"name":"Thyroid Section, Division of Endocrinology, Hypertension, and Diabetes, The Brigham and Women's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,2,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2012.02.002"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23116"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2015.0020"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03346587"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2009.0274"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000339959"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1309\/8VL9-ECXY-NVMX-2RQF"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.20029"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000658-199809000-00005"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00423-008-0366-7"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1067\/msy.2001.118370"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20000701)89:1<202::AID-CNCR27>3.0.CO;2-A"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP12183.RA"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21612"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010-1087"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1203208"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2010.0243"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP14066.PS"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-2658"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2482"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-3584"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPIX52MBOKTICP"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/dc.21790"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1159\/000333232"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.20091"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPO0BQ2YSKPXXP"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/dc.23052"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP13330.OR"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21455"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2015.0049"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.13.10537"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/dc.10043"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.0386"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/dc.23378"},{"key":"e_1_2_8_36_1","first-page":"3996","article-title":"Wide inter\u2010institutional variation in performance of a molecular classifier for indeterminate thyroid nodules. Ann Surg","volume":"22","author":"Marti JL","year":"2015","journal-title":"Oncol"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21624"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21749"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1159\/000446797"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP161231.OR"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2015.0505"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21411"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21412"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPEIE12POICULI"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0280"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/dc.23559"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/dc.21292"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncy.21305"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1159\/000334218"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-159-5-201309030-00006"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0247"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-3396"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-015-0419-z"}],"container-title":["Cancer Cytopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncy.21827","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncy.21827","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T16:40:36Z","timestamp":1760287236000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncy.21827"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,2]]},"references-count":52,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["10.1002\/cncy.21827"],"URL":"https:\/\/doi.org\/10.1002\/cncy.21827","archive":["Portico"],"relation":{},"ISSN":["1934-662X","1934-6638"],"issn-type":[{"value":"1934-662X","type":"print"},{"value":"1934-6638","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,2]]}}}