{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T23:02:50Z","timestamp":1762642970447,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T00:00:00Z","timestamp":1706313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese funds","award":["SFRH\/BD\/147650\/2019"],"award-info":[{"award-number":["SFRH\/BD\/147650\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Introduction: Molecular tests can contribute to improve the preoperative diagnosis of thyroid nodules. Tests available are expensive and not adapted to different populations. Aim: This study aimed to compare the cyto-histological genetic profile and to evaluate the reliability of molecular tests using ultrasound-guided fine needle aspiration cytology (US-FNAC) in accurately diagnosing differentiated thyroid carcinomas (DTCs) and predicting biologic behavior of papillary thyroid carcinomas (PTCs). Materials and Methods: The series included 259 patients with paired cyto-histological samples totaling 518 samples. The genetic alterations were analyzed via PCR\/Sanger sequencing. The association with clinicopathologic features was evaluated in PTCs. Results\/Discussion: From the 259 patients included, histologies were 50 (19.3%) benign controls and 209 (80.7%) DTC cases, from which 182 were PTCs; cytologies were 5.8% non-diagnostic, 18.2% benign, 39% indeterminate, and 37.1% malignant. In histology, indeterminate nodules (n = 101) were 22.8% benign and 77.2% malignant. Mutation frequencies in cytology and histology specimens were, respectively, TERTp: 3.7% vs. 7.9%; BRAF: 19.5% vs. 25.1%; and RAS: 11% vs. 17.5%. The overall cyto-histological agreement of the genetic mutations was 94.9%, with Cohen\u2019s k = 0.67, and in indeterminate nodules agreement was 95.7%, k = 0.64. The identified mutations exhibited a discriminative ability in diagnosing DTC with a specificity of 100% for TERTp and BRAF, and of 94% for RAS, albeit with low sensitivity. TERTp and BRAF mutations were associated with aggressive clinicopathological features and tumor progression in PTCs (p &lt; 0.001). The obtained good cyto-histological agreement suggests that molecular analysis via US-FNAC may anticipate the genetic profile and the behavior of thyroid tumors, confirming malignancy and contributing to referring patients to surgery.<\/jats:p>","DOI":"10.3390\/diagnostics14030278","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T08:54:03Z","timestamp":1706518443000},"page":"278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Comparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid Carcinomas"],"prefix":"10.3390","volume":"14","author":[{"given":"Maria de Lurdes","family":"Matos","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolismo, Centro Hospitalar Universit\u00e1rio de Lisboa Central, Hospital Curry Cabral, 1050-099 Lisbon, Portugal"}]},{"given":"Mafalda","family":"Pinto","sequence":"additional","affiliation":[{"name":"Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), i3S\u2014Institute for Research & Innovation in Health, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7421-8550","authenticated-orcid":false,"given":"Marta","family":"Alves","sequence":"additional","affiliation":[{"name":"Gabinete de Estat\u00edstica do Centro de Investiga\u00e7\u00e3o do Centro Hospitalar Universit\u00e1rio de Lisboa Central, EPE, Nova Medical School, 1169-045 Lisbon, Portugal"},{"name":"Centro de Estat\u00edstica e Aplica\u00e7\u00f5es da Universidade de Lisboa (CEAUL), 1749-016 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3736-1323","authenticated-orcid":false,"given":"Sule","family":"Canberk","sequence":"additional","affiliation":[{"name":"Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), i3S\u2014Institute for Research & Innovation in Health, 4200-135 Porto, Portugal"}]},{"given":"Ana","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Department of Pathology, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0357-7350","authenticated-orcid":false,"given":"Maria Jo\u00e3o","family":"Bugalho","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Centro Hospitalar Universit\u00e1rio de Lisboa Norte, Hospital de Santa Maria, 1649-028 Lisboa, Portugal"},{"name":"Medical Faculty, University of Lisbon, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2918-8364","authenticated-orcid":false,"given":"Ana Lu\u00edsa","family":"Papoila","sequence":"additional","affiliation":[{"name":"Gabinete de Estat\u00edstica do Centro de Investiga\u00e7\u00e3o do Centro Hospitalar Universit\u00e1rio de Lisboa Central, EPE, Nova Medical School, 1169-045 Lisbon, Portugal"},{"name":"Centro de Estat\u00edstica e Aplica\u00e7\u00f5es da Universidade de Lisboa (CEAUL), 1749-016 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9607-6998","authenticated-orcid":false,"given":"Paula","family":"Soares","sequence":"additional","affiliation":[{"name":"Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), i3S\u2014Institute for Research & Innovation in Health, 4200-135 Porto, Portugal"},{"name":"Medical Faculty, University of Porto, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1111\/j.1365-2265.1977.tb01340.x","article-title":"The spectrum of thyroid disease in a community: The Whickham survey","volume":"7","author":"Tunbridge","year":"1977","journal-title":"Clin. 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