{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:11:47Z","timestamp":1787069507628,"version":"build-2736575974"},"reference-count":41,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Cytopathological evaluation of thyroid fine-needle aspiration biopsy (FNAB) specimens can fail to raise preoperative suspicion of medullary thyroid carcinoma (MTC). The Afirma RNA-sequencing MTC classifier identifies MTC among FNA samples that are cytologically indeterminate, suspicious, or malignant (Bethesda categories III\u2013VI). In this study we report the development and clinical performance of this MTC classifier.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Algorithm training was performed with a set of 483 FNAB specimens (21 MTC and 462 non-MTC). A support vector machine classifier was developed using 108 differentially expressed genes, which includes the 5 genes in the prior Afirma microarray-based MTC cassette.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>The final MTC classifier was blindly tested on 211 preoperative FNAB specimens with subsequent surgical pathology, including 21 MTC and 190 non-MTC specimens from benign and malignant thyroid nodules independent from those used in training. The classifier had 100% sensitivity (21\/21 MTC FNAB specimens correctly called positive; 95% confidence interval [CI]\u2009=\u200983.9\u2013100%) and 100% specificity (190\/190 non-MTC FNAs correctly called negative; CI\u2009=\u200998.1\u2013100%). All positive samples had pathological confirmation of MTC, while all negative samples were negative for MTC on surgical pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The RNA-sequencing MTC classifier accurately identified MTC from preoperative thyroid nodule FNAB specimens in an independent validation cohort. This identification may facilitate an MTC-specific preoperative evaluation and resulting treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2022.0189","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T11:32:38Z","timestamp":1657107158000},"page":"1069-1076","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":30,"title":["Preoperative Identification of Medullary Thyroid Carcinoma (MTC): Clinical Validation of the Afirma MTC RNA-Sequencing Classifier"],"prefix":"10.1177","volume":"32","author":[{"given":"Gregory W.","family":"Randolph","sequence":"first","affiliation":[{"name":"Division of Thyroid and Parathyroid Endocrine Surgery, Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie Ann","family":"Sosa","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of California San Francisco (UCSF), San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangyang","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Veracyte, Inc., South San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor E.","family":"Angell","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Keck School of Medicine, University of Southern California, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":", Jr.","given":"David C.","family":"Shonka","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2014Head and Neck Surgery, University of Virginia, Charlottesville, Virginia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia A.","family":"LiVolsi","sequence":"additional","affiliation":[{"name":"Anatomic Pathology Division, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W.","family":"Ladenson","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Blevins","sequence":"additional","affiliation":[{"name":"Texas Diabetes and Endocrinology, Austin, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7947-4393","authenticated-orcid":false,"given":"Quan-Yang","family":"Duh","sequence":"additional","affiliation":[{"name":"Section of Endocrine Surgery, Department of Surgery, University of California San Francisco, San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Ghossein","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mack","family":"Harrell","sequence":"additional","affiliation":[{"name":"The Memorial Center for Integrative Endocrine Surgery, Hollywood, Weston and Boca Raton, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kepal Narendra","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Endocrine Surgery, Department of Surgery, NYU Langone Medical Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Shanik","sequence":"additional","affiliation":[{"name":"Endocrine Associates of Long Island, Smithtown, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Thomas","family":"Traweek","sequence":"additional","affiliation":[{"name":"Thyroid Cytopathology Partners, Austin, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Sean","family":"Walsh","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Veracyte, Inc., South San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Yeh","sequence":"additional","affiliation":[{"name":"Section of Endocrine Surgery, UCLA David Geffen School of Medicine, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5611-5833","authenticated-orcid":false,"given":"Amr H.","family":"Abdelhamid Ahmed","sequence":"additional","affiliation":[{"name":"Division of Thyroid and Parathyroid Endocrine Surgery, Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5423-509X","authenticated-orcid":false,"given":"Allen S.","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Cedars-Sinai Medical Center, Los Angeles, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Wong","sequence":"additional","affiliation":[{"name":"Head and Neck Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua P.","family":"Klopper","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Veracyte, Inc., South San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Veracyte, Inc., South San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia C.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Veracyte, Inc., South San Francisco, California, USA."},{"name":"Department of Medical Affairs, Veracyte, Inc., South San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4183-7387","authenticated-orcid":false,"given":"Richard T.","family":"Kloos","sequence":"additional","affiliation":[{"name":"Department of Medical Affairs, Veracyte, Inc., South San Francisco, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Sadow","sequence":"additional","affiliation":[{"name":"Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Massachusetts Eye and Ear, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,9,14]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2014.0335"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2016.04.053"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/hed.26550"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/cen.12563"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.4158\/EP13143.OR"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-010-1017-0"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11845-016-1455-1"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1998.00392.x"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2013.03.443"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021713"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2016.0001"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12444"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2018.1153"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0378-3758(02)00388-9"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1203208"},{"key":"e_1_3_6_17_2","unstructured":"Amin MB American Joint Committee on Cancer American Cancer Society. 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