{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:03:15Z","timestamp":1792184595314,"version":"4.4.0"},"reference-count":57,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T00:00:00Z","timestamp":1623715200000},"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>Background: non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), which is considered as low-risk cancer, should be distinguished from the malignant invasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). Improved discrimination of NIFTPs from invasive EFVPTCs using a molecular biomarker test could provide useful insights into pre- and post-surgical management of the indeterminate thyroid nodule. Galectin-3 (Gal-3), a \u03b2-galactosyl-binding molecule in the lectin group, is involved in different biological functions in well differentiated thyroid carcinomas. The aim of this study was to determine whether Gal-3 expression as a diagnostic marker could distinguish indolent NIFTP from invasive EFVPTC on tissue specimens from surgical thyroid nodules. Methods: immunohistochemical (IHC) analysis of cytoplasmic and nuclear Gal-3 expression was performed in formalin-fixed paraffin-embedded (FFPE) surgical tissues in four specific diagnostic subgroups- benign nodules, NIFTPs, EFVPTCs and lymphocytic\/Hashimoto\u2019s thyroiditis (LTs). Results: cytoplasmic Gal-3 expression (mean \u00b1 SD) was significantly increased in invasive EFVPTCs (4.80 \u00b1 1.60) compared to NIFTPs (2.75 \u00b1 1.58, p &lt; 0.001) and benign neoplasms (2.09 \u00b1 1.19, p &lt; 0.001) with no significant difference between NIFTPs and benign lesions (p = 0.064). The presence of LT enhanced cytoplasmic Gal-3 expression (3.80 \u00b1 1.32) compared to NIFTPs (p = 0.016) and benign nodules (p &lt; 0.001). Nuclear Gal-3 expression in invasive EFVPTCs (1.84 \u00b1 1.30) was significantly higher than in NIFTPs (1.00 \u00b1 0.72, p = 0.001), but similar to benign nodules (1.44 \u00b1 1.77, p = 0.215), thereby obviating its potential clinical application. Conclusions: our observations have indicated that increased cytoplasmic Gal-3 expression shows diagnostic potential in distinguishing NIFTP among encapsulated follicular variant nodules thereby serving as a possible ancillary test to H&amp;E histopathological diagnostic criteria when LT interference is absent, to assist in the detection of the invasive EFVPTC among such nodules.<\/jats:p>","DOI":"10.3390\/cancers13122988","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T11:00:33Z","timestamp":1623754833000},"page":"2988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Diagnostic Value of Galectin-3 in Distinguishing Invasive Encapsulated Carcinoma from Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features (NIFTP)"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8896-3949","authenticated-orcid":false,"given":"Guodong","family":"Fu","sequence":"first","affiliation":[{"name":"Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0705-7977","authenticated-orcid":false,"given":"Olena","family":"Polyakova","sequence":"additional","affiliation":[{"name":"Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald S.","family":"Chazen","sequence":"additional","affiliation":[{"name":"Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy L.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Sinai Health System, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada"},{"name":"Department of Otolaryngology-Head and Neck Surgery, Sinai Health System, Mount Sinai Hospital, University of Toronto, Toronto, ON M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian J.","family":"Witterick","sequence":"additional","affiliation":[{"name":"Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada"},{"name":"Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Sinai Health System, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada"},{"name":"Department of Otolaryngology-Head and Neck Surgery, Sinai Health System, Mount Sinai Hospital, University of Toronto, Toronto, ON M5G 1X5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1001\/jama.2017.2719","article-title":"Trends in Thyroid Cancer Incidence and Mortality in the United States, 1974\u20132013","volume":"317","author":"Lim","year":"2017","journal-title":"JAMA"},{"key":"ref_2","unstructured":"The Surveillance E, and End Results (SEER) Program (2020, June 02). 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