Fatores histopatológicos e moleculares em retinoblastomas enucleados

Detalhes bibliográficos
Ano de defesa: 2013
Autor(a) principal: Salustiano, Luciana Ximenes lattes
Orientador(a): Ávila, Marcos Pereira de lattes
Banca de defesa: Ávila, Marcos Pereira de, Carneiro, Fabiana P., Saddi, Vera A., Mendonça, Elismauro F. de, Cruvinel, Davi Isaac
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Goiás
Programa de Pós-Graduação: Programa de Pós-graduação em Ciências da Saúde (FM)
Departamento: Faculdade de Medicina - FM (RG)
País: Brasil
Palavras-chave em Português:
P16
Área do conhecimento CNPq:
Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tede/3247
Resumo: Retinoblastoma (RB) is the malignant neoplasm of embryonic neural retinal cells and is the most common intraocular tumor of childhood. Early diagnosis associated with modern methods of treatment resulted in increased survival rate of patients with retinoblastoma. However, in those cases whose diagnosis is delayed and in untreated cases, the disease is invariably fatal. The knowledge of the molecular and histopathological features of retinoblastomas can influence the choice of treatment and benefit the prognosis of these tumors. Thus, the objectives of this study are to evaluate the main histopathological and molecular characteristics of retinoblastomas, including the evaluation of p16, Ki67 and VEGF protein expression, as well as the potential role of such molecules as prognostic markers in the retinoblastomas. Fifty-seven cases of RB were evaluated in enucleated eyes at Hospital Araújo Jorge, in Goiânia, in the period of 1998 to 2011. Clinical data were collected from the respective medical files and the cases were reviewed for analysis of histopathological aspects. The expression of Ki67, p16 and VEGF was assessed by immunohistochemistry, using specific antibodies and a detection system associated with polymers. The results were analyzed by descriptive statistics and categorical variables by chi-square test and Fisher exact test, when necessary. Ki67 overexpression was observed in 28% of cases, characterizing the retinoblastomas with high rate of cellular proliferation, while the p16 overexpression was observed in 42% of retinoblastomas evaluated. Significant associations were observed between the overexpression of these proteins and histopathological characteristics of worse prognosis, including invasion of the optic nerve, choroid, sclera and anterior chamber of the eye, as well as to a lower degree of cellular differentiation. VEGF expression was extensively observed in all retinoblastoma cases, independent of the histopathological aspects of the tumors. The associations observed in this study between tumor aggressive histopathological aspects and Ki67 and p16 overexpression, indicate the use of these markers in determining the prognosis of retinoblastomas. On the other hand, the high angiogenic potential of retinoblastomas, translated by diffuse VEGF expression in all cases analyzed in this study, raises new investigations on the use of anti-angiogenic drugs in the treatment of retinoblastomas.
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spelling Ávila, Marcos Pereira dehttp://lattes.cnpq.br/3335187297522447Saddi, Vera AparecidaÁvila, Marcos Pereira deCarneiro, Fabiana P.Saddi, Vera A.Mendonça, Elismauro F. deCruvinel, Davi Isaachttp://lattes.cnpq.br/8052402241776628Salustiano, Luciana Ximenes2014-10-01T15:33:57Z2013-12-17SALUSTIANO, Luciana Ximenes. Fatores histopatológicos e moleculares em retinoblastomas enucleados. 2013. 64 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Goiás, Goiânia, 2013.http://repositorio.bc.ufg.br/tede/handle/tede/3247Retinoblastoma (RB) is the malignant neoplasm of embryonic neural retinal cells and is the most common intraocular tumor of childhood. Early diagnosis associated with modern methods of treatment resulted in increased survival rate of patients with retinoblastoma. However, in those cases whose diagnosis is delayed and in untreated cases, the disease is invariably fatal. The knowledge of the molecular and histopathological features of retinoblastomas can influence the choice of treatment and benefit the prognosis of these tumors. Thus, the objectives of this study are to evaluate the main histopathological and molecular characteristics of retinoblastomas, including the evaluation of p16, Ki67 and VEGF protein expression, as well as the potential role of such molecules as prognostic markers in the retinoblastomas. Fifty-seven cases of RB were evaluated in enucleated eyes at Hospital Araújo Jorge, in Goiânia, in the period of 1998 to 2011. Clinical data were collected from the respective medical files and the cases were reviewed for analysis of histopathological aspects. The expression of Ki67, p16 and VEGF was assessed by immunohistochemistry, using specific antibodies and a detection system associated with polymers. The results were analyzed by descriptive statistics and categorical variables by chi-square test and Fisher exact test, when necessary. Ki67 overexpression was observed in 28% of cases, characterizing the retinoblastomas with high rate of cellular proliferation, while the p16 overexpression was observed in 42% of retinoblastomas evaluated. Significant associations were observed between the overexpression of these proteins and histopathological characteristics of worse prognosis, including invasion of the optic nerve, choroid, sclera and anterior chamber of the eye, as well as to a lower degree of cellular differentiation. VEGF expression was extensively observed in all retinoblastoma cases, independent of the histopathological aspects of the tumors. The associations observed in this study between tumor aggressive histopathological aspects and Ki67 and p16 overexpression, indicate the use of these markers in determining the prognosis of retinoblastomas. On the other hand, the high angiogenic potential of retinoblastomas, translated by diffuse VEGF expression in all cases analyzed in this study, raises new investigations on the use of anti-angiogenic drugs in the treatment of retinoblastomas.O retinoblastoma (RB) é o tumor maligno das células neurais embrionárias da retina e consiste no tumor intraocular mais comum da infância. O diagnóstico precoce associado a modernos métodos de tratamento resultou em aumento da taxa da sobrevida de pacientes com retinoblastoma. No entanto, nos casos cujo diagnóstico é tardio e nos casos não tratados, a doença é invariavelmente fatal. O conhecimento das características histopatológicas e moleculares dos retinoblastomas pode direcionar a escolha do tratamento e beneficiar o prognóstico desses tumores. Este estudo objetiva avaliar as principais características histopatológicas e moleculares dos retinoblastomas, incluindo a avaliação da expressão das proteínas p16, Ki67 e VEGF e o potencial papel prognóstico desses marcadores que são anticorpos envolvidos na carcinogênese, angiogênese e proliferação celular. Cinquenta e sete casos de RB foram avaliados em olhos enucleados no Hospital Araújo Jorge, em Goiânia, no período de 1998 a 2011. Os dados clínicos foram coletados dos respectivos prontuários e todos os casos foram revistos para análise dos aspectos histopatológicos. A expressão de Ki67, p16 e VEGF foi avaliada por imunoistoquímica, utilizando anticorpos específicos e sistema de detecção associado a polímeros. Os resultados foram analisados por estatística descritiva e as variáveis categóricas pelo teste do qui-quadrado e teste exato de Fisher, quando necessário. A superexpressão de Ki67 foi observada em 28% dos casos, caracterizando os retinoblastomas com alto índice de proliferação celular, enquanto a superexpressão de p16 foi observada em 42% dos retinoblastomas avaliados. Associações significativas foram detectadas entre a superexpressão dessas proteínas e as características histopatológicas de pior prognóstico, incluindo invasão do nervo óptico, esclera, coroide e câmara anterior do olho, bem como ao menor grau de diferenciação celular. A expressão de VEGF foi observada de forma difusa em todos os casos analisados, independente dos aspectos histopatológicos dos tumores. As associações observadas neste estudo, entre os aspectos histopatológicos de maior agressividade tumoral e a superexpressão de Ki67 e p16, indicam que o uso destes marcadores pode influir na determinação do prognóstico dos retinoblastomas. Por outro lado, o alto potencial angiogênico dos retinoblastomas, traduzido pela expressão difusa do VEGF em todos os casos analisados neste estudo, suscita novas investigações sobre o uso de medicamentos anti-angiogênicos no tratamento dos retinoblastomas.application/pdfhttp://repositorio.bc.ufg.br/tede/retrieve/9204/Tese%20-%20%20Luciana%20Ximenes%20Salustiano%20-%202013.pdf.jpgporUniversidade Federal de GoiásPrograma de Pós-graduação em Ciências da Saúde (FM)UFGBrasilFaculdade de Medicina - FM (RG)http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessRetinoblastomaHistopatológicoMunoistoquímicaP16Ki67VEGFRetinoblastomasHistopathological characteristicsImmunohistochemistryCIENCIAS DA SAUDE::MEDICINAFatores histopatológicos e moleculares em retinoblastomas enucleadosHistopathological and molecular factors in enucleated retinoblastomasinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis-10068643126177453106006006001545772475950486338-969369452308786627reponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGLICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv Fatores histopatológicos e moleculares em retinoblastomas enucleados
dc.title.alternative.eng.fl_str_mv Histopathological and molecular factors in enucleated retinoblastomas
title Fatores histopatológicos e moleculares em retinoblastomas enucleados
spellingShingle Fatores histopatológicos e moleculares em retinoblastomas enucleados
Salustiano, Luciana Ximenes
Retinoblastoma
Histopatológico
Munoistoquímica
P16
Ki67
VEGF
Retinoblastomas
Histopathological characteristics
Immunohistochemistry
CIENCIAS DA SAUDE::MEDICINA
title_short Fatores histopatológicos e moleculares em retinoblastomas enucleados
title_full Fatores histopatológicos e moleculares em retinoblastomas enucleados
title_fullStr Fatores histopatológicos e moleculares em retinoblastomas enucleados
title_full_unstemmed Fatores histopatológicos e moleculares em retinoblastomas enucleados
title_sort Fatores histopatológicos e moleculares em retinoblastomas enucleados
author Salustiano, Luciana Ximenes
author_facet Salustiano, Luciana Ximenes
author_role author
dc.contributor.advisor1.fl_str_mv Ávila, Marcos Pereira de
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/3335187297522447
dc.contributor.advisor-co1.fl_str_mv Saddi, Vera Aparecida
dc.contributor.referee1.fl_str_mv Ávila, Marcos Pereira de
dc.contributor.referee2.fl_str_mv Carneiro, Fabiana P.
dc.contributor.referee3.fl_str_mv Saddi, Vera A.
dc.contributor.referee4.fl_str_mv Mendonça, Elismauro F. de
dc.contributor.referee5.fl_str_mv Cruvinel, Davi Isaac
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/8052402241776628
dc.contributor.author.fl_str_mv Salustiano, Luciana Ximenes
contributor_str_mv Ávila, Marcos Pereira de
Saddi, Vera Aparecida
Ávila, Marcos Pereira de
Carneiro, Fabiana P.
Saddi, Vera A.
Mendonça, Elismauro F. de
Cruvinel, Davi Isaac
dc.subject.por.fl_str_mv Retinoblastoma
Histopatológico
Munoistoquímica
P16
Ki67
VEGF
Retinoblastomas
Histopathological characteristics
Immunohistochemistry
topic Retinoblastoma
Histopatológico
Munoistoquímica
P16
Ki67
VEGF
Retinoblastomas
Histopathological characteristics
Immunohistochemistry
CIENCIAS DA SAUDE::MEDICINA
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::MEDICINA
description Retinoblastoma (RB) is the malignant neoplasm of embryonic neural retinal cells and is the most common intraocular tumor of childhood. Early diagnosis associated with modern methods of treatment resulted in increased survival rate of patients with retinoblastoma. However, in those cases whose diagnosis is delayed and in untreated cases, the disease is invariably fatal. The knowledge of the molecular and histopathological features of retinoblastomas can influence the choice of treatment and benefit the prognosis of these tumors. Thus, the objectives of this study are to evaluate the main histopathological and molecular characteristics of retinoblastomas, including the evaluation of p16, Ki67 and VEGF protein expression, as well as the potential role of such molecules as prognostic markers in the retinoblastomas. Fifty-seven cases of RB were evaluated in enucleated eyes at Hospital Araújo Jorge, in Goiânia, in the period of 1998 to 2011. Clinical data were collected from the respective medical files and the cases were reviewed for analysis of histopathological aspects. The expression of Ki67, p16 and VEGF was assessed by immunohistochemistry, using specific antibodies and a detection system associated with polymers. The results were analyzed by descriptive statistics and categorical variables by chi-square test and Fisher exact test, when necessary. Ki67 overexpression was observed in 28% of cases, characterizing the retinoblastomas with high rate of cellular proliferation, while the p16 overexpression was observed in 42% of retinoblastomas evaluated. Significant associations were observed between the overexpression of these proteins and histopathological characteristics of worse prognosis, including invasion of the optic nerve, choroid, sclera and anterior chamber of the eye, as well as to a lower degree of cellular differentiation. VEGF expression was extensively observed in all retinoblastoma cases, independent of the histopathological aspects of the tumors. The associations observed in this study between tumor aggressive histopathological aspects and Ki67 and p16 overexpression, indicate the use of these markers in determining the prognosis of retinoblastomas. On the other hand, the high angiogenic potential of retinoblastomas, translated by diffuse VEGF expression in all cases analyzed in this study, raises new investigations on the use of anti-angiogenic drugs in the treatment of retinoblastomas.
publishDate 2013
dc.date.issued.fl_str_mv 2013-12-17
dc.date.accessioned.fl_str_mv 2014-10-01T15:33:57Z
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dc.identifier.citation.fl_str_mv SALUSTIANO, Luciana Ximenes. Fatores histopatológicos e moleculares em retinoblastomas enucleados. 2013. 64 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Goiás, Goiânia, 2013.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tede/3247
identifier_str_mv SALUSTIANO, Luciana Ximenes. Fatores histopatológicos e moleculares em retinoblastomas enucleados. 2013. 64 f. Tese (Doutorado em Ciências da Saúde) - Universidade Federal de Goiás, Goiânia, 2013.
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