High Prevalence of BRAF Mutation in a Brazilian Cohort of Patients With Sporadic Papillary Thyroid Carcinomas Correlation With More Aggressive Phenotype and Decreased Expression of Iodide-Metabolizing Genes
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/31330 http://dx.doi.org/10.1002/cncr.24118 |
Resumo: | BACKGROUND: Although several studies undoubtedly demonstrated that BRAF mutation is an important genetic event in the pathogenesis of papillary thyroid carcinoma (PTC), its prognostic significance and correlation with less differentiated states remains unclear. It has been suggested that the discrepancy may be at least partially due to the insufficient number of cases analyzed, epidemiologic factors, and a combination of different variants of PTC included in these studies. METHODS: in this context, the prevalence of the BRAF mutation in a Brazilian cohort of PTCs (n = 120) was first assessed and correlated with clinicopathologic features. the BRAF exon 15 mutation was evaluated by direct sequencing. Furthermore, using quantitative polymerase chain reaction, the issue of whether the expression level of the iodide-metabolizing genes (NIS and TSHR) was correlated with BRAF mutational status was investigated. RESULTS: A high prevalence of the BRAF mutation was found in PTC cases (48%). the BRAF mutation was found to be significantly associated with the classic variant of PTC (66%; P < .0001), although it was found in the follicular variant as well (21%). Subtype stratification demonstrated that the BRAF V600E mutation was associated with tumor size, extrathyroid invasion, the presence of lymph node metastasis and risk of disease recurrence, and mortality in patients with the classic variant of PTC. Moreover, the expression levels of NIS and TSHR were remarkably lower in PTCs harboring the BRAF V600E mutation. CONCLUSIONS: These findings provide further evidence that BRAF might be associated with a more aggressive phenotype and less differentiated state due to decreased expression of iodide-metabolizing genes. the search for a BRAF mutation in the current study population appears to be valuable for predicting prognosis and guiding management in patients with PTC. Cancer 2009;115:972-80. (c) 2009 American Cancer Society. |
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Oler, Gisele [UNIFESP]Cerutti, Janete Maria [UNIFESP]Universidade Federal de São Paulo (UNIFESP)2016-01-24T13:52:17Z2016-01-24T13:52:17Z2009-03-01Cancer. Hoboken: Wiley-Blackwell, v. 115, n. 5, p. 972-980, 2009.0008-543Xhttp://repositorio.unifesp.br/handle/11600/31330http://dx.doi.org/10.1002/cncr.2411810.1002/cncr.24118WOS:000263593500008BACKGROUND: Although several studies undoubtedly demonstrated that BRAF mutation is an important genetic event in the pathogenesis of papillary thyroid carcinoma (PTC), its prognostic significance and correlation with less differentiated states remains unclear. It has been suggested that the discrepancy may be at least partially due to the insufficient number of cases analyzed, epidemiologic factors, and a combination of different variants of PTC included in these studies. METHODS: in this context, the prevalence of the BRAF mutation in a Brazilian cohort of PTCs (n = 120) was first assessed and correlated with clinicopathologic features. the BRAF exon 15 mutation was evaluated by direct sequencing. Furthermore, using quantitative polymerase chain reaction, the issue of whether the expression level of the iodide-metabolizing genes (NIS and TSHR) was correlated with BRAF mutational status was investigated. RESULTS: A high prevalence of the BRAF mutation was found in PTC cases (48%). the BRAF mutation was found to be significantly associated with the classic variant of PTC (66%; P < .0001), although it was found in the follicular variant as well (21%). Subtype stratification demonstrated that the BRAF V600E mutation was associated with tumor size, extrathyroid invasion, the presence of lymph node metastasis and risk of disease recurrence, and mortality in patients with the classic variant of PTC. Moreover, the expression levels of NIS and TSHR were remarkably lower in PTCs harboring the BRAF V600E mutation. CONCLUSIONS: These findings provide further evidence that BRAF might be associated with a more aggressive phenotype and less differentiated state due to decreased expression of iodide-metabolizing genes. the search for a BRAF mutation in the current study population appears to be valuable for predicting prognosis and guiding management in patients with PTC. Cancer 2009;115:972-80. (c) 2009 American Cancer Society.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Genet Bases Thyroid Tumor Lab, Div Endocrinol, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Div Genet, Genet Bases Thyroid Tumor Lab, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Genet Bases Thyroid Tumor Lab, Div Endocrinol, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Div Genet, Genet Bases Thyroid Tumor Lab, BR-04039032 São Paulo, BrazilFAPESP: 05/60330-8Web of Science972-980engWiley-BlackwellCancerhttp://olabout.wiley.com/WileyCDA/Section/id-406071.htmlinfo:eu-repo/semantics/openAccesspapillary thyroid carcinomaclinicopathologic featuresBRAFNISTSHRHigh Prevalence of BRAF Mutation in a Brazilian Cohort of Patients With Sporadic Papillary Thyroid Carcinomas Correlation With More Aggressive Phenotype and Decreased Expression of Iodide-Metabolizing Genesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlereponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/313302022-07-08 11:07:23.595metadata only accessoai:repositorio.unifesp.br:11600/31330Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-07-08T14:07:23Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
High Prevalence of BRAF Mutation in a Brazilian Cohort of Patients With Sporadic Papillary Thyroid Carcinomas Correlation With More Aggressive Phenotype and Decreased Expression of Iodide-Metabolizing Genes |
title |
High Prevalence of BRAF Mutation in a Brazilian Cohort of Patients With Sporadic Papillary Thyroid Carcinomas Correlation With More Aggressive Phenotype and Decreased Expression of Iodide-Metabolizing Genes |
spellingShingle |
High Prevalence of BRAF Mutation in a Brazilian Cohort of Patients With Sporadic Papillary Thyroid Carcinomas Correlation With More Aggressive Phenotype and Decreased Expression of Iodide-Metabolizing Genes Oler, Gisele [UNIFESP] papillary thyroid carcinoma clinicopathologic features BRAF NIS TSHR |
title_short |
High Prevalence of BRAF Mutation in a Brazilian Cohort of Patients With Sporadic Papillary Thyroid Carcinomas Correlation With More Aggressive Phenotype and Decreased Expression of Iodide-Metabolizing Genes |
title_full |
High Prevalence of BRAF Mutation in a Brazilian Cohort of Patients With Sporadic Papillary Thyroid Carcinomas Correlation With More Aggressive Phenotype and Decreased Expression of Iodide-Metabolizing Genes |
title_fullStr |
High Prevalence of BRAF Mutation in a Brazilian Cohort of Patients With Sporadic Papillary Thyroid Carcinomas Correlation With More Aggressive Phenotype and Decreased Expression of Iodide-Metabolizing Genes |
title_full_unstemmed |
High Prevalence of BRAF Mutation in a Brazilian Cohort of Patients With Sporadic Papillary Thyroid Carcinomas Correlation With More Aggressive Phenotype and Decreased Expression of Iodide-Metabolizing Genes |
title_sort |
High Prevalence of BRAF Mutation in a Brazilian Cohort of Patients With Sporadic Papillary Thyroid Carcinomas Correlation With More Aggressive Phenotype and Decreased Expression of Iodide-Metabolizing Genes |
author |
Oler, Gisele [UNIFESP] |
author_facet |
Oler, Gisele [UNIFESP] Cerutti, Janete Maria [UNIFESP] |
author_role |
author |
author2 |
Cerutti, Janete Maria [UNIFESP] |
author2_role |
author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Oler, Gisele [UNIFESP] Cerutti, Janete Maria [UNIFESP] |
dc.subject.eng.fl_str_mv |
papillary thyroid carcinoma clinicopathologic features BRAF NIS TSHR |
topic |
papillary thyroid carcinoma clinicopathologic features BRAF NIS TSHR |
description |
BACKGROUND: Although several studies undoubtedly demonstrated that BRAF mutation is an important genetic event in the pathogenesis of papillary thyroid carcinoma (PTC), its prognostic significance and correlation with less differentiated states remains unclear. It has been suggested that the discrepancy may be at least partially due to the insufficient number of cases analyzed, epidemiologic factors, and a combination of different variants of PTC included in these studies. METHODS: in this context, the prevalence of the BRAF mutation in a Brazilian cohort of PTCs (n = 120) was first assessed and correlated with clinicopathologic features. the BRAF exon 15 mutation was evaluated by direct sequencing. Furthermore, using quantitative polymerase chain reaction, the issue of whether the expression level of the iodide-metabolizing genes (NIS and TSHR) was correlated with BRAF mutational status was investigated. RESULTS: A high prevalence of the BRAF mutation was found in PTC cases (48%). the BRAF mutation was found to be significantly associated with the classic variant of PTC (66%; P < .0001), although it was found in the follicular variant as well (21%). Subtype stratification demonstrated that the BRAF V600E mutation was associated with tumor size, extrathyroid invasion, the presence of lymph node metastasis and risk of disease recurrence, and mortality in patients with the classic variant of PTC. Moreover, the expression levels of NIS and TSHR were remarkably lower in PTCs harboring the BRAF V600E mutation. CONCLUSIONS: These findings provide further evidence that BRAF might be associated with a more aggressive phenotype and less differentiated state due to decreased expression of iodide-metabolizing genes. the search for a BRAF mutation in the current study population appears to be valuable for predicting prognosis and guiding management in patients with PTC. Cancer 2009;115:972-80. (c) 2009 American Cancer Society. |
publishDate |
2009 |
dc.date.issued.fl_str_mv |
2009-03-01 |
dc.date.accessioned.fl_str_mv |
2016-01-24T13:52:17Z |
dc.date.available.fl_str_mv |
2016-01-24T13:52:17Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Cancer. Hoboken: Wiley-Blackwell, v. 115, n. 5, p. 972-980, 2009. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/31330 http://dx.doi.org/10.1002/cncr.24118 |
dc.identifier.issn.none.fl_str_mv |
0008-543X |
dc.identifier.doi.none.fl_str_mv |
10.1002/cncr.24118 |
dc.identifier.wos.none.fl_str_mv |
WOS:000263593500008 |
identifier_str_mv |
Cancer. Hoboken: Wiley-Blackwell, v. 115, n. 5, p. 972-980, 2009. 0008-543X 10.1002/cncr.24118 WOS:000263593500008 |
url |
http://repositorio.unifesp.br/handle/11600/31330 http://dx.doi.org/10.1002/cncr.24118 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Cancer |
dc.rights.driver.fl_str_mv |
http://olabout.wiley.com/WileyCDA/Section/id-406071.html info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://olabout.wiley.com/WileyCDA/Section/id-406071.html |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
972-980 |
dc.publisher.none.fl_str_mv |
Wiley-Blackwell |
publisher.none.fl_str_mv |
Wiley-Blackwell |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764160071630848 |