{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:31:24Z","timestamp":1790796684579,"version":"4.1.0"},"reference-count":26,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,11]],"date-time":"2022-12-11T00:00:00Z","timestamp":1670716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The risk of malignancy (ROM) of EIF1AX-mutated thyroid nodules has been theorized to be contingent on the position of the mutation within the gene and the presence of co-existing mutations. However, due to EIF1AX\u2019s low mutation frequency, sample sizes currently reported in the literature are too diminutive to appraise the clinical utility of molecular diagnostic testing. The objective of this study was to elucidate prognostic indicators of EIF1AX-mutated thyroid tumors and cancer aggressiveness by examining a large cohort of cytologically indeterminate thyroid nodules (CITNs) that underwent molecular testing and subsequent surgical resection. This is a multicenter study involving 764 subtotal and total thyroidectomy patients that underwent preoperative molecular testing at two quaternary care hospitals. A five-year retrospective review was performed on the 42 charts of patients that opted for surgery following a positive EIF1AX mutation on ThyroseqV3 results from January 2018 to May 2022. Patient demographics, cytopathology results, molecular testing results, and postoperative histopathology were reviewed. Of the 42 surgically resected nodules that harbored an EIF1AX mutation, 16 (38.1%) were benign, six (14.3%) were non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) or well-differentiated thyroid neoplasms of uncertain malignant potential (WDT-UMPs), and 20 (47.6%) were malignant. An isolated EIF1AX mutation conferred a ROM of 47.6%, whereas the ROM for nodules with at least one additional molecular alteration was 72.7%. The ROM increased to 100% for nodules with at least one additional molecular alteration and the A113_splice site mutation. Six malignant nodules were aggressive, with five having variegated components of poorly differentiated thyroid carcinoma (PDTC). EIF1AX-mutated thyroid nodules are more susceptible to malignancy in the presence of the A113_splice site mutation and when co-mutated with RAS and\/or TP53. This deleterious amalgam is associated with aggressive disease and renders these nodules PDTC. A preoperative molecular test finding of an EIF1AX mutation can be a useful tool for thyroid specialists to optimize clinical management.<\/jats:p>","DOI":"10.3390\/cancers14246097","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T04:34:20Z","timestamp":1670819660000},"page":"6097","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Prognostic Indicators of EIF1AX-Mutated Thyroid Tumor Malignancy and Cancer Aggressiveness"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3763-2119","authenticated-orcid":false,"given":"Saruchi","family":"Bandargal","sequence":"first","affiliation":[{"name":"Faculty of Medicine, McGill University, Montreal, QC H3G 2M1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, University of Toronto, Toronto, ON M5S, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6490-4189","authenticated-orcid":false,"given":"Marc Philippe","family":"Pusztaszeri","sequence":"additional","affiliation":[{"name":"Department of Pathology, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique-Isabelle","family":"Forest","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina Daniela","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J.","family":"Payne","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, McGill University, Jewish General Hospital, Montreal, QC H3T 1E2, Canada"},{"name":"Department of Otolaryngology\u2013Head and Neck Surgery, McGill University, Royal Victoria Hospital, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S2213-8587(21)00049-8","article-title":"A worldwide journey of thyroid cancer incidence centred on tumour histology","volume":"9","author":"Rossi","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_2","unstructured":"(2021). 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