{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:42:49Z","timestamp":1787316169629,"version":"build-2736575974"},"reference-count":21,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Journal of Otolaryngology - Head & Neck Surgery"],"published-print":{"date-parts":[[2026,1]]},"abstract":"\n Importance<\/jats:title>\n \n BRAF V600E<\/jats:italic>\n mutations are frequently associated with aggressive papillary thyroid carcinomas (PTCs), yet tumors with low allele frequency (AF) are often considered to be indolent. However, exceptions exist, suggesting additional factors may influence tumor behavior. Gene expression alterations (GEA) may help identify tumors with more aggressive molecular phenotypes.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To evaluate whether aggressive clinicopathologic features are associated with GEA positivity in low AF\n BRAF V600E<\/jats:italic>\n -mutated PTCs.\n <\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n Retrospective cohort study.<\/jats:p>\n <\/jats:sec>\n \n Setting<\/jats:title>\n Two McGill University Academic Hospitals, 2019 to 2024.<\/jats:p>\n <\/jats:sec>\n \n Participants<\/jats:title>\n \n Patients with PTC harboring\n BRAF V600E<\/jats:italic>\n (AF\u2009\u2264\u200925%) who underwent preoperative testing.\n <\/jats:p>\n <\/jats:sec>\n \n Intervention or Exposure<\/jats:title>\n \n Low AF\n BRAF V600E<\/jats:italic>\n mutation (\u226425%) characterized using ThyroSeq v3 genomic classifier.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcome Measures<\/jats:title>\n The primary outcome was GEA status. Tumor aggressiveness (defined by extrathyroidal extension, lymph node metastasis, lymphovascular invasion, high-risk histology, or aggressive variants), Bethesda classification, and AF were evaluated as predictors of GEA using logistic regression. Stratified analysis was performed based on AF (\u226410% vs. >10%).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Among 49 patients identified (mean age 49\u2009\u00b1\u200914\u2009years; 86% female; mean AF 11%\u2009\u00b1\u20098%), 73% (36\/49) had aggressive features and 61% (30\/49) had GEA-positive tumors. Among GEA-positive tumors, 80% (24\/30) were classified as aggressive and had a significantly-higher median AF (16.5%) than GEA-negative tumors (\n P<\/jats:italic>\n \u2009=\u2009.0003). Stratified analysis showed that Bethesda VI nodules significantly predicted GEA positivity in tumors with AF\u2009>\u200910% (\n P<\/jats:italic>\n \u2009=\u2009.03).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n In low AF BRAF V600E-mutated PTCs, GEA positivity is associated with high-risk cytology, higher AF, and aggressive tumor features.<\/jats:p>\n <\/jats:sec>\n \n Relevance<\/jats:title>\n GEA may be a useful molecular marker of aggressive tumor biology in low AF PTCs and holds potential as a complementary tool for preoperative risk stratification.<\/jats:p>\n <\/jats:sec>","DOI":"10.1177\/19160216251409738","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T12:04:43Z","timestamp":1767873883000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Association of Gene Expression Alterations with Aggressive Features in Papillary Thyroid Carcinomas Harboring Low Allele Frequency BRAF V600E Mutations"],"prefix":"10.1177","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7137-6393","authenticated-orcid":false,"given":"Alexandra","family":"Katz","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coralie","family":"Lefebvre","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-2119","authenticated-orcid":false,"given":"Saruchi","family":"Bandargal","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, McGill University, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique-Isabelle","family":"Forest","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, McGill University, Royal Victoria Hospital, Montreal, QC, Canada"},{"name":"Department of Otolaryngology-Head and Neck Surgery, McGill University, Jewish General Hospital, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc Philippe","family":"Pusztaszeri","sequence":"additional","affiliation":[{"name":"Department of Pathology, McGill University, Jewish General Hospital, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Payne","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, McGill University, Royal Victoria Hospital, Montreal, QC, Canada"},{"name":"Department of Otolaryngology-Head and Neck Surgery, McGill University, Jewish General Hospital, Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1177\/0300060519873481"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1530\/EC-21-0410"},{"key":"e_1_3_3_4_2","first-page":"25","article-title":"Molecular targeting of the BRAF proto-oncogene\/mitogen-activated protein kinase (MAPK) pathway across cancers","author":"Shan KS","year":"2024","unstructured":"Shan KS, Rehman TU, Ivanov S, et al. Molecular targeting of the BRAF proto-oncogene\/mitogen-activated protein kinase (MAPK) pathway across cancers. Int J Mol Sci 2024;25(1):624.","journal-title":"Int J Mol Sci"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2104"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.3190"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16010113"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgae774"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15010049"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.6819"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/bcr2222"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-817218-6.00008-5"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad181"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-3106"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-020-01391-1"},{"key":"e_1_3_3_16_2","volume-title":"WHO Classification of Tumours of Endocrine Organs","author":"Lloyd RV","year":"2017","unstructured":"Lloyd RV, Osamura RY, Kl\u00f6ppel GJR. WHO Classification of Tumours of Endocrine Organs. 4th ed. World Health Organization; 2017.","edition":"4"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1530\/EC-18-0333"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2013.0573"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-013-3076-5"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/hed.24466"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/coa.13859"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2015.0020"}],"container-title":["Journal of Otolaryngology - Head & Neck Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/19160216251409738","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/19160216251409738","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/19160216251409738","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T22:54:21Z","timestamp":1777589661000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/19160216251409738"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":21,"alternative-id":["10.1177\/19160216251409738"],"URL":"https:\/\/doi.org\/10.1177\/19160216251409738","relation":{},"ISSN":["1916-0216","1916-0216"],"issn-type":[{"value":"1916-0216","type":"print"},{"value":"1916-0216","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"article-number":"19160216251409738"}}