Estudo da associação entre a acromegalia e a presença da mutação BRAFV600E e a expressão imunohistoquímica de IGF-1 e galectina-3 no carcinoma papilífero de tireoide

Detalhes bibliográficos
Autor(a) principal: Montenegro, Renan Magalhães
Data de Publicação: 2012
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/3845
Resumo: Epidemiological studies suggest that thyroid carcinoma is the most common malignant neoplasm in acromegalic patients. At this moment there are no reports of studies evaluating molecular markers of papillary thyroid carcinoma (PTC) in this population. OBJECTIVES: The present work aimed to evaluate the association between acromegaly, expression of the mutation BRAFV600E, immunohistochemical markers (galectin-3 and IGF-1), and clinical-pathological characteristics in acromegalic patients with PTC. MATERIALS AND METHODS: This is a cross-sectional study conducted from January/09 to December/2011, where 11 acromegalic patients with CPT, from 5 Brazilian centers of reference in the treatment of acromegaly were compared with 45 patients with acromegaly without PTC. We evaluated clinical and histopathological variables of PTC. We used histological PTC embedded in paraffin for mutation study BRAFV600E and immunohistochemical analysis of markers IGF-1 and galectin-3. In the analysis we used the Student t test and chi-square test (SPSS software, version 13.0 for Windows) (p <0.05). RESULTS: The average age of acromegalic patients with PTC was 61.5 ± 6.02 years and 72.7% were female. The average time of diagnosis of acromegaly was 7.7 ± 3.90 years, and the interval between diagnosis of acromegaly and PTC was an average 3.4 ± 2.71 years. The serum levels of IGF-1 in the diagnosis of acromegaly PTC was 417.0 ng / mL. There was no difference in the TNM (Tumor, Nodule, Metastasis) and AMES prognostic index (Ages, Metastasis, Extent, Size) between groups. There was a higher prevalence of the BRAFV600E mutation (90.9% vs 55.6%, p = 0.039) and stronger immunohistochemical expression for IGF-1 (88.9% vs 38.1%, p = 0.017) in acromegaly. There was no difference in the expression of galectin-3 between the groups. CONCLUSION: This work for the first time showed a high prevalence of mutations in BRAFV600E in PTC of acromegalic patients superior to those described in the population with PTC in this and previous studies (approximately 40%). However, this mutation was not associated with a more aggressive tumor phenotype, which differs from the findings in acromegalic population without PTC. We conclude that acromegaly is possibly associated to a mutation BRAFV600E in acromegalic patients with CPT. Further studies are needed to define the mechanisms responsible for this association.
id UFC-7_3e1978d707c4d0fede3aafe78656d4aa
oai_identifier_str oai:repositorio.ufc.br:riufc/3845
network_acronym_str UFC-7
network_name_str Repositório Institucional da Universidade Federal do Ceará (UFC)
repository_id_str
spelling Estudo da associação entre a acromegalia e a presença da mutação BRAFV600E e a expressão imunohistoquímica de IGF-1 e galectina-3 no carcinoma papilífero de tireoideStudy of the association between acromegaly and the presence of BRAFV600E mutation and immunohistochemical expression of IGF-1 and galectin-3 in papillary thyroid carcinomaAcromegaliaEpidemiological studies suggest that thyroid carcinoma is the most common malignant neoplasm in acromegalic patients. At this moment there are no reports of studies evaluating molecular markers of papillary thyroid carcinoma (PTC) in this population. OBJECTIVES: The present work aimed to evaluate the association between acromegaly, expression of the mutation BRAFV600E, immunohistochemical markers (galectin-3 and IGF-1), and clinical-pathological characteristics in acromegalic patients with PTC. MATERIALS AND METHODS: This is a cross-sectional study conducted from January/09 to December/2011, where 11 acromegalic patients with CPT, from 5 Brazilian centers of reference in the treatment of acromegaly were compared with 45 patients with acromegaly without PTC. We evaluated clinical and histopathological variables of PTC. We used histological PTC embedded in paraffin for mutation study BRAFV600E and immunohistochemical analysis of markers IGF-1 and galectin-3. In the analysis we used the Student t test and chi-square test (SPSS software, version 13.0 for Windows) (p <0.05). RESULTS: The average age of acromegalic patients with PTC was 61.5 ± 6.02 years and 72.7% were female. The average time of diagnosis of acromegaly was 7.7 ± 3.90 years, and the interval between diagnosis of acromegaly and PTC was an average 3.4 ± 2.71 years. The serum levels of IGF-1 in the diagnosis of acromegaly PTC was 417.0 ng / mL. There was no difference in the TNM (Tumor, Nodule, Metastasis) and AMES prognostic index (Ages, Metastasis, Extent, Size) between groups. There was a higher prevalence of the BRAFV600E mutation (90.9% vs 55.6%, p = 0.039) and stronger immunohistochemical expression for IGF-1 (88.9% vs 38.1%, p = 0.017) in acromegaly. There was no difference in the expression of galectin-3 between the groups. CONCLUSION: This work for the first time showed a high prevalence of mutations in BRAFV600E in PTC of acromegalic patients superior to those described in the population with PTC in this and previous studies (approximately 40%). However, this mutation was not associated with a more aggressive tumor phenotype, which differs from the findings in acromegalic population without PTC. We conclude that acromegaly is possibly associated to a mutation BRAFV600E in acromegalic patients with CPT. Further studies are needed to define the mechanisms responsible for this association.Estudos epidemiológicos sugerem que o carcinoma de tireoide seja a neoplasia maligna mais frequente nos pacientes acromegálicos. Até este momento não há relatos de estudos avaliando marcadores moleculares do carcinoma papilífero de tireoide (CPT) nessa população. OBJETIVOS: Avaliar a associação entre acromegalia, presença da mutação BRAFV600E, marcadores imunohistoquímicos (galectina-3 e IGF-1) e características clínico-patológicas em pacientes acromegálicos com CPT. MATERIAL E MÉTODOS: Trata-se de um estudo transversal realizado no período de janeiro/09 a dezembro/2011, onde 11 pacientes acromegálicos com CPT, provenientes de 5 centros brasileiros de referência no tratamento da acromegalia foram comparados com 45 pacientes com CPT sem acromegalia. Foram estudadas variáveis clínicas e histopatológicas do CPT. Utilizou-se cortes histológicos de CPT emblocados em parafina para o estudo da mutação BRAFV600E e para a análise imunohistoquímica dos marcadores IGF-1 e galectina-3. Na análise utilizou-se os testes t de student e do qui-quadrado (software SPSS, versão 13.0 para Windows) (p<0,05). RESULTADOS: A idade média dos pacientes acromegálicos com CPT foi de 61,5 ± 6,02 anos, sendo 72,7% do sexo feminino. O tempo médio de diagnóstico da acromegalia foi de 7,7 ± 3,90 anos, sendo o intervalo entre o diagnóstico da acromegalia e do CPT, em média, 3,4 ± 2,71 anos. Os níveis séricos de IGF-1 dos acromegálicos ao diagnóstico do CPT foi de 417,0 ng/mL. Não houve diferença quanto ao estadiamento TNM (Tumor, Nodule, Metastasis) e índice prognóstico AMES (Ages, Metastasis, Extent, Size) entre os grupos. Houve maior prevalência da mutação BRAFV600E (90,9% vs 55,6%; p=0,039) e de forte imunoexpressão para IGF-1 (88,9% vs 38,1%; p= 0,017) nos acromegálicos. Não houve diferença na expressão de galectina-3 entre os grupos. CONCLUSÃO: Neste trabalho, pela primeira vez se mostrou uma alta prevalência da mutação BRAFV600E em CPT de acromegálicos, muito superior à descrita na população com CPT neste e em estudos anteriores (cerca de 40%). Contudo essa mutação não se mostrou associada a um fenótipo mais agressivo do tumor, o que diverge dos achados em população não acromegálica com CPT. Conclui-se que a acromegalia é possivelmente associada à mutação BRAFV600E em pacientes acromegálicos com CPT. Novos estudos serão necessários para definir os mecanismos responsáveis por tal associação.Moraes, Maria Elisabete Amaral deKimura, Edna TerukoMontenegro, Renan Magalhães2012-10-01T16:30:58Z2012-10-01T16:30:58Z2012info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfMONTENEGRO, R. M. Estudo da associação entre a acromegalia e a presença da mutação BRAFV600E e a expressão imunohistoquímica de IGF-1 e galectina-3 no carcinoma papilífero de tireoide. 2012. 72 f. Tese (Doutorado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2012.http://www.repositorio.ufc.br/handle/riufc/3845porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2019-11-10T22:28:36Zoai:repositorio.ufc.br:riufc/3845Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:22:19.271124Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Estudo da associação entre a acromegalia e a presença da mutação BRAFV600E e a expressão imunohistoquímica de IGF-1 e galectina-3 no carcinoma papilífero de tireoide
Study of the association between acromegaly and the presence of BRAFV600E mutation and immunohistochemical expression of IGF-1 and galectin-3 in papillary thyroid carcinoma
title Estudo da associação entre a acromegalia e a presença da mutação BRAFV600E e a expressão imunohistoquímica de IGF-1 e galectina-3 no carcinoma papilífero de tireoide
spellingShingle Estudo da associação entre a acromegalia e a presença da mutação BRAFV600E e a expressão imunohistoquímica de IGF-1 e galectina-3 no carcinoma papilífero de tireoide
Montenegro, Renan Magalhães
Acromegalia
title_short Estudo da associação entre a acromegalia e a presença da mutação BRAFV600E e a expressão imunohistoquímica de IGF-1 e galectina-3 no carcinoma papilífero de tireoide
title_full Estudo da associação entre a acromegalia e a presença da mutação BRAFV600E e a expressão imunohistoquímica de IGF-1 e galectina-3 no carcinoma papilífero de tireoide
title_fullStr Estudo da associação entre a acromegalia e a presença da mutação BRAFV600E e a expressão imunohistoquímica de IGF-1 e galectina-3 no carcinoma papilífero de tireoide
title_full_unstemmed Estudo da associação entre a acromegalia e a presença da mutação BRAFV600E e a expressão imunohistoquímica de IGF-1 e galectina-3 no carcinoma papilífero de tireoide
title_sort Estudo da associação entre a acromegalia e a presença da mutação BRAFV600E e a expressão imunohistoquímica de IGF-1 e galectina-3 no carcinoma papilífero de tireoide
author Montenegro, Renan Magalhães
author_facet Montenegro, Renan Magalhães
author_role author
dc.contributor.none.fl_str_mv Moraes, Maria Elisabete Amaral de
Kimura, Edna Teruko
dc.contributor.author.fl_str_mv Montenegro, Renan Magalhães
dc.subject.por.fl_str_mv Acromegalia
topic Acromegalia
description Epidemiological studies suggest that thyroid carcinoma is the most common malignant neoplasm in acromegalic patients. At this moment there are no reports of studies evaluating molecular markers of papillary thyroid carcinoma (PTC) in this population. OBJECTIVES: The present work aimed to evaluate the association between acromegaly, expression of the mutation BRAFV600E, immunohistochemical markers (galectin-3 and IGF-1), and clinical-pathological characteristics in acromegalic patients with PTC. MATERIALS AND METHODS: This is a cross-sectional study conducted from January/09 to December/2011, where 11 acromegalic patients with CPT, from 5 Brazilian centers of reference in the treatment of acromegaly were compared with 45 patients with acromegaly without PTC. We evaluated clinical and histopathological variables of PTC. We used histological PTC embedded in paraffin for mutation study BRAFV600E and immunohistochemical analysis of markers IGF-1 and galectin-3. In the analysis we used the Student t test and chi-square test (SPSS software, version 13.0 for Windows) (p <0.05). RESULTS: The average age of acromegalic patients with PTC was 61.5 ± 6.02 years and 72.7% were female. The average time of diagnosis of acromegaly was 7.7 ± 3.90 years, and the interval between diagnosis of acromegaly and PTC was an average 3.4 ± 2.71 years. The serum levels of IGF-1 in the diagnosis of acromegaly PTC was 417.0 ng / mL. There was no difference in the TNM (Tumor, Nodule, Metastasis) and AMES prognostic index (Ages, Metastasis, Extent, Size) between groups. There was a higher prevalence of the BRAFV600E mutation (90.9% vs 55.6%, p = 0.039) and stronger immunohistochemical expression for IGF-1 (88.9% vs 38.1%, p = 0.017) in acromegaly. There was no difference in the expression of galectin-3 between the groups. CONCLUSION: This work for the first time showed a high prevalence of mutations in BRAFV600E in PTC of acromegalic patients superior to those described in the population with PTC in this and previous studies (approximately 40%). However, this mutation was not associated with a more aggressive tumor phenotype, which differs from the findings in acromegalic population without PTC. We conclude that acromegaly is possibly associated to a mutation BRAFV600E in acromegalic patients with CPT. Further studies are needed to define the mechanisms responsible for this association.
publishDate 2012
dc.date.none.fl_str_mv 2012-10-01T16:30:58Z
2012-10-01T16:30:58Z
2012
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv MONTENEGRO, R. M. Estudo da associação entre a acromegalia e a presença da mutação BRAFV600E e a expressão imunohistoquímica de IGF-1 e galectina-3 no carcinoma papilífero de tireoide. 2012. 72 f. Tese (Doutorado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2012.
http://www.repositorio.ufc.br/handle/riufc/3845
identifier_str_mv MONTENEGRO, R. M. Estudo da associação entre a acromegalia e a presença da mutação BRAFV600E e a expressão imunohistoquímica de IGF-1 e galectina-3 no carcinoma papilífero de tireoide. 2012. 72 f. Tese (Doutorado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2012.
url http://www.repositorio.ufc.br/handle/riufc/3845
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal do Ceará (UFC)
instname:Universidade Federal do Ceará (UFC)
instacron:UFC
instname_str Universidade Federal do Ceará (UFC)
instacron_str UFC
institution UFC
reponame_str Repositório Institucional da Universidade Federal do Ceará (UFC)
collection Repositório Institucional da Universidade Federal do Ceará (UFC)
repository.name.fl_str_mv Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)
repository.mail.fl_str_mv bu@ufc.br || repositorio@ufc.br
_version_ 1813028775653277696