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Comparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid Carcinomas

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Resumo: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’s 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 < 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.
Autores principais:Matos, Maria de Lurdes
Outros Autores:Pinto, Mafalda; Alves, Marta; Alves, Marta; Canberk, Sule; Canberk, Sule; Gonçalves, Ana; Bugalho, Maria João; Bugalho, Maria João; Papoila, Ana Luísa; Papoila, A.L.; Soares, Paula; Soares, Paula
Assunto:BRAF differentiated thyroid carcinomas (DTCs) genetics indeterminate nodules papillary thyroid carcinomas (PTCs) RAS TERT ultrasound-guided fine needle aspiration cytology (US-FNAC) Clinical Biochemistry
Ano:2024
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade Nova de Lisboa
Idioma:inglês
Origem:Repositório Institucional da UNL
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author Matos, Maria de Lurdes
author2 Pinto, Mafalda
Alves, Marta
Alves, Marta
Canberk, Sule
Canberk, Sule
Gonçalves, Ana
Bugalho, Maria João
Bugalho, Maria João
Papoila, Ana Luísa
Papoila, A.L.
Soares, Paula
Soares, Paula
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author_facet Matos, Maria de Lurdes
Pinto, Mafalda
Alves, Marta
Alves, Marta
Canberk, Sule
Canberk, Sule
Gonçalves, Ana
Bugalho, Maria João
Bugalho, Maria João
Papoila, Ana Luísa
Papoila, A.L.
Soares, Paula
Soares, Paula
author_role author
contributor_name_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
MDPI - Multidisciplinary Digital Publishing Institute
RUN
country_str PT
creators_json_txt [{\"Person.name\":\"Matos, Maria de Lurdes\"},{\"Person.name\":\"Pinto, Mafalda\"},{\"Person.name\":\"Alves, Marta\"},{\"Person.name\":\"Alves, Marta\",\"Person.identifier.orcid\":\"0000-0002-7421-8550\"},{\"Person.name\":\"Canberk, Sule\"},{\"Person.name\":\"Canberk, Sule\",\"Person.identifier.orcid\":\"0000-0002-3736-1323\"},{\"Person.name\":\"Gonçalves, Ana\"},{\"Person.name\":\"Bugalho, Maria João\"},{\"Person.name\":\"Bugalho, Maria João\",\"Person.identifier.orcid\":\"0000-0003-0357-7350\"},{\"Person.name\":\"Papoila, Ana Luísa\"},{\"Person.name\":\"Papoila, A.L.\",\"Person.identifier.orcid\":\"0000-0002-2918-8364\"},{\"Person.name\":\"Soares, Paula\"},{\"Person.name\":\"Soares, Paula\",\"Person.identifier.orcid\":\"0000-0001-9607-6998\"}]
datacite.contributors.contributor.contributorName.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
MDPI - Multidisciplinary Digital Publishing Institute
RUN
datacite.creators.creator.creatorName.fl_str_mv Matos, Maria de Lurdes
Pinto, Mafalda
Alves, Marta
Alves, Marta
Canberk, Sule
Canberk, Sule
Gonçalves, Ana
Bugalho, Maria João
Bugalho, Maria João
Papoila, Ana Luísa
Papoila, A.L.
Soares, Paula
Soares, Paula
datacite.date.Accepted.fl_str_mv 2024-02-01T00:00:00Z
datacite.date.available.fl_str_mv 2024-03-07T00:00:05Z
datacite.date.embargoed.fl_str_mv 2024-03-07T00:00:05Z
datacite.rights.fl_str_mv http://purl.org/coar/access_right/c_abf2
datacite.subjects.subject.fl_str_mv BRAF
differentiated thyroid carcinomas (DTCs)
genetics
indeterminate nodules
papillary thyroid carcinomas (PTCs)
RAS
TERT
ultrasound-guided fine needle aspiration cytology (US-FNAC)
Clinical Biochemistry
datacite.titles.title.fl_str_mv Comparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid Carcinomas
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
MDPI - Multidisciplinary Digital Publishing Institute
RUN
dc.creator.none.fl_str_mv Matos, Maria de Lurdes
Pinto, Mafalda
Alves, Marta
Alves, Marta
Canberk, Sule
Canberk, Sule
Gonçalves, Ana
Bugalho, Maria João
Bugalho, Maria João
Papoila, Ana Luísa
Papoila, A.L.
Soares, Paula
Soares, Paula
dc.date.Accepted.fl_str_mv 2024-02-01T00:00:00Z
dc.date.available.fl_str_mv 2024-03-07T00:00:05Z
dc.date.embargoed.fl_str_mv 2024-03-07T00:00:05Z
dc.format.none.fl_str_mv application/pdf
dc.identifier.none.fl_str_mv http://hdl.handle.net/10362/164575
dc.language.none.fl_str_mv eng
dc.rights.none.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.subject.none.fl_str_mv BRAF
differentiated thyroid carcinomas (DTCs)
genetics
indeterminate nodules
papillary thyroid carcinomas (PTCs)
RAS
TERT
ultrasound-guided fine needle aspiration cytology (US-FNAC)
Clinical Biochemistry
dc.title.fl_str_mv Comparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid Carcinomas
dc.type.none.fl_str_mv http://purl.org/coar/resource_type/c_6501
description 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’s 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 < 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.
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eu_rights_str_mv openAccess
format article
fulltext.url.fl_str_mv https://run.unl.pt/bitstreams/a7e15958-8c83-4943-adfd-1edf9969240d/download
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institution Universidade Nova de Lisboa
instname_str Universidade Nova de Lisboa
language eng
network_acronym_str run
network_name_str Repositório Institucional da UNL
oai_identifier_str oai:run.unl.pt:10362/164575
organization_str_mv urn:organizationAcronym:unl
person_str_mv Matos, Maria de Lurdes
Pinto, Mafalda
Alves, Marta
Alves, Marta
Alves, Marta
https://www.ciencia-id.pt/851A-750C-73C2
851A-750C-73C2
http://orcid.org/0000-0002-7421-8550
0000-0002-7421-8550
Canberk, Sule
Canberk, Sule
Canberk, Sule
https://www.ciencia-id.pt/2F1A-4173-9A5B
2F1A-4173-9A5B
http://orcid.org/0000-0002-3736-1323
0000-0002-3736-1323
Gonçalves, Ana
Bugalho, Maria João
Bugalho, Maria João
Bugalho, Maria João
https://www.ciencia-id.pt/D51C-30D5-71FC
D51C-30D5-71FC
http://orcid.org/0000-0003-0357-7350
0000-0003-0357-7350
Papoila, Ana Luísa
Papoila, A.L.
Papoila, A.L.
https://www.ciencia-id.pt/251C-0273-1068
251C-0273-1068
http://orcid.org/0000-0002-2918-8364
0000-0002-2918-8364
Soares, Paula
Soares, Paula
Soares, Paula
https://www.ciencia-id.pt/571D-96F7-0457
571D-96F7-0457
http://orcid.org/0000-0001-9607-6998
0000-0001-9607-6998
publishDate 2024
reponame_str Repositório Institucional da UNL
repository_id_str urn:repositoryAcronym:run
service_str_mv urn:repositoryAcronym:run
spelling engenIntroduction: 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’s 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 < 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.application/pdfenComparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid CarcinomasMatos, Maria de LurdesPinto, MafaldaAlves, MartaPersonalAlves, MartaDSpacehttp://dspace.org/items/f09bebb2-3725-45e4-af7d-3cac4bc2b06bDSpacehttp://dspace.org/items/f09bebb2-3725-45e4-af7d-3cac4bc2b06bAlvesMartaCiência IDhttps://www.ciencia-id.pt851A-750C-73C2ORCIDhttp://orcid.org0000-0002-7421-8550Researcher IDhttps://www.researcherid.comP-2486-2016Scopus Author IDhttps://www.scopus.com55762063400Canberk, SulePersonalCanberk, SuleDSpacehttp://dspace.org/items/a7fc6cc3-dd33-4fe0-ad50-1af47aa6628dDSpacehttp://dspace.org/items/a7fc6cc3-dd33-4fe0-ad50-1af47aa6628dcanberksuleCiência IDhttps://www.ciencia-id.pt2F1A-4173-9A5BORCIDhttp://orcid.org0000-0002-3736-1323Scopus Author IDhttps://www.scopus.com15842998100Gonçalves, AnaBugalho, Maria JoãoPersonalBugalho, Maria JoãoDSpacehttp://dspace.org/items/939c1772-e72e-4641-b0fa-e375aff67bc1DSpacehttp://dspace.org/items/939c1772-e72e-4641-b0fa-e375aff67bc1BugalhoMaria JoãoCiência IDhttps://www.ciencia-id.ptD51C-30D5-71FCORCIDhttp://orcid.org0000-0003-0357-7350Scopus Author IDhttps://www.scopus.com35582359500Papoila, Ana LuísaPersonalPapoila, A.L.DSpacehttp://dspace.org/items/5ce1bd05-e7a4-4bd0-9527-f511c0889095DSpacehttp://dspace.org/items/5ce1bd05-e7a4-4bd0-9527-f511c0889095PapoilaAna LuisaCiência IDhttps://www.ciencia-id.pt251C-0273-1068ORCIDhttp://orcid.org0000-0002-2918-8364Researcher IDhttps://www.researcherid.comS-2515-2016Scopus Author IDhttps://www.scopus.com6507532321Soares, PaulaPersonalSoares, PaulaDSpacehttp://dspace.org/items/a98dc4f7-a5f2-448b-8221-43cea1ae11dbDSpacehttp://dspace.org/items/a98dc4f7-a5f2-448b-8221-43cea1ae11dbSoaresPaulaCiência IDhttps://www.ciencia-id.pt571D-96F7-0457ORCIDhttp://orcid.org0000-0001-9607-6998Researcher IDhttps://www.researcherid.comB-6054-2008Scopus Author IDhttps://www.scopus.com35478020200Scopus Author IDhttps://www.scopus.com57195213812NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)MDPI - Multidisciplinary Digital Publishing InstituteHostingInstitutionOrganizationalRUNe-mailmailto:run@unl.ptrun@unl.ptISSNIsPartOf2075-4418URNIsPartOfPURE: 84622533URNIsPartOfPURE UUID: afed6a04-a136-4b3d-aa90-418b00aedd98URNIsPartOfScopus: 85184683629DOIIsPartOf10.3390/diagnostics140302782024-03-07T00:00:05Z2024-022024-02-01T00:00:00ZHandlehttp://hdl.handle.net/10362/164575http://purl.org/coar/access_right/c_abf2open accessBRAFdifferentiated thyroid carcinomas (DTCs)geneticsindeterminate nodulespapillary thyroid carcinomas (PTCs)RASTERTultrasound-guided fine needle aspiration cytology (US-FNAC)Clinical Biochemistry302248 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://run.unl.pt/bitstreams/a7e15958-8c83-4943-adfd-1edf9969240d/download
spellingShingle Comparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid Carcinomas
Matos, Maria de Lurdes
BRAF
differentiated thyroid carcinomas (DTCs)
genetics
indeterminate nodules
papillary thyroid carcinomas (PTCs)
RAS
TERT
ultrasound-guided fine needle aspiration cytology (US-FNAC)
Clinical Biochemistry
status SINGLETON
subject.fl_str_mv BRAF
differentiated thyroid carcinomas (DTCs)
genetics
indeterminate nodules
papillary thyroid carcinomas (PTCs)
RAS
TERT
ultrasound-guided fine needle aspiration cytology (US-FNAC)
Clinical Biochemistry
title Comparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid Carcinomas
title_full Comparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid Carcinomas
title_fullStr Comparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid Carcinomas
title_full_unstemmed Comparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid Carcinomas
title_short Comparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid Carcinomas
title_sort Comparative Cyto-Histological Genetic Profile in a Series of Differentiated Thyroid Carcinomas
topic BRAF
differentiated thyroid carcinomas (DTCs)
genetics
indeterminate nodules
papillary thyroid carcinomas (PTCs)
RAS
TERT
ultrasound-guided fine needle aspiration cytology (US-FNAC)
Clinical Biochemistry
topic_facet BRAF
differentiated thyroid carcinomas (DTCs)
genetics
indeterminate nodules
papillary thyroid carcinomas (PTCs)
RAS
TERT
ultrasound-guided fine needle aspiration cytology (US-FNAC)
Clinical Biochemistry
url http://hdl.handle.net/10362/164575
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