Immunohistochemical evaluation of angiogenesis markers VEGF and Angipoietin-2 in Hepatocellular Carcinoma and precursor lesions of cirrhotic explants

Detalhes bibliográficos
Autor(a) principal: Andrà Costa Teixeira
Data de Publicação: 2016
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFC
Texto Completo: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=16477
Resumo: Hepatocellular carcinoma (HCC) is a global health problem and is associated with chronic liver disease, especially in the cirrhotic phase. This tumor can be preceded by precursor lesions, namely low and high grade dysplastic nodules, and regenerative nodules, typical of cirrhosis. The current study evaluated the immunohistochemical expression of VEGF and angiopoietin-2 in HCC and precursor lesions is a single institution series of liver explants between 2013-2015 using tissue microarray methods. Immunohistochemical variables were correlated with angiogenesis and prognostic parameters. 107 nodules from 67 patients were studied, including 26 HCC and 5 dysplastic nodules. There was no significant epidemiologic difference between HCC, dysplastic nodules and regenerative nodule groups. Angiopoietin-2 was significantly more expressed in HCC nodules when compared with regenerative lesions (p < 0,0001*). VEGF and Ang-2 expression correlated with each other (p=0,006) and with number of unpaired arteries within nodules (p=0,03 â VEGF) and with the percentage of CD34 positive sinusoids (p < 0,0001 â VEGF and p< 0,007 â Ang-2). There was no significant correlation between any of the immunohistochemical parameters with clinical staging, number of gross lesions and histologic grade in cases of HCC. Angiopoietin-2 had a sensitivity of 54% and 96,25% of specificity for HCC diagnosis, and VEGF had a sensitivity of 69,23% and specificity of 31,25%. Our study shows that Ang-2 may be a good marker for HCC diagnosis when compared to others that are routinely used for this purpose. VEGF is not a good marker due to its lack of specificity, although other studies showed that it may be associated with prognostic parameters. Finally, our data reinforce the importance of angiogenesis evalutation in the development of HCC and its potential applicability as a diagnostic tool.
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spelling info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisImmunohistochemical evaluation of angiogenesis markers VEGF and Angipoietin-2 in Hepatocellular Carcinoma and precursor lesions of cirrhotic explantsAvaliaÃÃo imuno-histoquÃmica dos marcadores de angiogÃnese VEGF e angiopoietina-2 em carcinoma hepatocelular e lesÃes precursoras em explantes de pacientes cirrÃticos2016-02-24Fabio Rocha Fernandes TÃvora80063829304http://lattes.cnpq.br/5995375126302920Paulo Roberto Carvalho de Almeida11969130300http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4702849Y9Ivelise Regina Canito Brasil30931339391Ivelise Regina Canito BrasilJosà Telmo ValenÃa JÃnior4383924034406188030684http://lattes.cnpq.br/6115237686268421Andrà Costa TeixeiraUniversidade Federal do CearÃPrograma de PÃs-GraduaÃÃo em PatologiaUFCBRANATOMIA PATOLOGICA E PATOLOGIA CLINICAHepatocellular carcinoma (HCC) is a global health problem and is associated with chronic liver disease, especially in the cirrhotic phase. This tumor can be preceded by precursor lesions, namely low and high grade dysplastic nodules, and regenerative nodules, typical of cirrhosis. The current study evaluated the immunohistochemical expression of VEGF and angiopoietin-2 in HCC and precursor lesions is a single institution series of liver explants between 2013-2015 using tissue microarray methods. Immunohistochemical variables were correlated with angiogenesis and prognostic parameters. 107 nodules from 67 patients were studied, including 26 HCC and 5 dysplastic nodules. There was no significant epidemiologic difference between HCC, dysplastic nodules and regenerative nodule groups. Angiopoietin-2 was significantly more expressed in HCC nodules when compared with regenerative lesions (p < 0,0001*). VEGF and Ang-2 expression correlated with each other (p=0,006) and with number of unpaired arteries within nodules (p=0,03 â VEGF) and with the percentage of CD34 positive sinusoids (p < 0,0001 â VEGF and p< 0,007 â Ang-2). There was no significant correlation between any of the immunohistochemical parameters with clinical staging, number of gross lesions and histologic grade in cases of HCC. Angiopoietin-2 had a sensitivity of 54% and 96,25% of specificity for HCC diagnosis, and VEGF had a sensitivity of 69,23% and specificity of 31,25%. Our study shows that Ang-2 may be a good marker for HCC diagnosis when compared to others that are routinely used for this purpose. VEGF is not a good marker due to its lack of specificity, although other studies showed that it may be associated with prognostic parameters. Finally, our data reinforce the importance of angiogenesis evalutation in the development of HCC and its potential applicability as a diagnostic tool. O carcinoma hepatocelular (CHC) constitui um problema de saÃde global e està relacionado a hepatopatias crÃnicas em fase de cirrose. Esta neoplasia à geralmente precedida por lesÃes precursoras denominadas nÃdulos displÃsicos de baixo grau (LGDN) e alto grau (HGDN), os quais por sua vez sÃo provenientes dos nÃdulos regenerativos (NR) tÃpicos da cirrose. Este trabalho avaliou a expressÃo imuno-histoquÃmica dos marcadores VEGF e Angiopoietina-2 no CHC e nas lesÃes precursoras de explantes de pacientes cirrÃticos transplantados no Hospital Geral de Fortaleza nos anos de 2013 a 2015, correlacionando esta expressÃo a outros parÃmetros de angiogÃnese e prognÃsticos. Foram incluÃdos no estudo 107 nÃdulos de 67 pacientes com CHC e/ou lesÃes precursoras para confecÃÃo de âtissue microarrayâ (TMA). NÃo houve diferenÃas demogrÃficas entre os pacientes com CHC e nÃdulos displÃsicos ou regenerativos. O marcador Angiopoietina-2 apresentou diferenÃa de imunoexpressÃo entre as classes de nÃdulos (p < 0,0001*), sendo maior nos pacientes com CHC. Os marcadores VEGF e Angiopoietina-2 mostraram correlaÃÃo significativa entre si (&#961;=0,006) e com outros parÃmetros, tais como nÃmero de artÃrias (p=0,03 para VEGF) e positividade à imuno-histoquÃmica para CD34 (p < 0,0001 para VEGF e p = 0,007 para Ang-2). NÃo houve associaÃÃo entre os marcadores avaliados e parÃmetros utilizados para determinaÃÃo de estadiamento e prognÃstico do CHC, tais como tamanho, nÃmero de lesÃes no explante e grau histolÃgico. A Angiopoietina-2 apresentou sensibilidade de 54% e especificidade de 96,25% para o diagnÃstico de malignidade, enquanto o VEGF apresentou sensibilidade de 69,23% e especificidade de 31,25%. Nosso estudo mostrou que a angiopoietina-2 representa um bom marcador para o diagnÃstico do CHC quando comparado aos que sÃo utilizados atualmente, enquanto o VEGF, embora tenha apresentado correlaÃÃo com parÃmetros prognÃsticos em outros estudos, nÃo se mostra um bom marcador por sua baixa especificidade. Por fim, os dados reforÃam a importÃncia de melhor avaliaÃÃo da angiogÃnese no desenvolvimento do CHC e seu papel no diagnÃstico anatomopatolÃgico destas lesÃes. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=16477application/pdfinfo:eu-repo/semantics/openAccessporreponame:Biblioteca Digital de Teses e Dissertações da UFCinstname:Universidade Federal do Cearáinstacron:UFC2019-01-21T11:29:46Zmail@mail.com -
dc.title.en.fl_str_mv Immunohistochemical evaluation of angiogenesis markers VEGF and Angipoietin-2 in Hepatocellular Carcinoma and precursor lesions of cirrhotic explants
dc.title.alternative.pt.fl_str_mv AvaliaÃÃo imuno-histoquÃmica dos marcadores de angiogÃnese VEGF e angiopoietina-2 em carcinoma hepatocelular e lesÃes precursoras em explantes de pacientes cirrÃticos
title Immunohistochemical evaluation of angiogenesis markers VEGF and Angipoietin-2 in Hepatocellular Carcinoma and precursor lesions of cirrhotic explants
spellingShingle Immunohistochemical evaluation of angiogenesis markers VEGF and Angipoietin-2 in Hepatocellular Carcinoma and precursor lesions of cirrhotic explants
Andrà Costa Teixeira
ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
title_short Immunohistochemical evaluation of angiogenesis markers VEGF and Angipoietin-2 in Hepatocellular Carcinoma and precursor lesions of cirrhotic explants
title_full Immunohistochemical evaluation of angiogenesis markers VEGF and Angipoietin-2 in Hepatocellular Carcinoma and precursor lesions of cirrhotic explants
title_fullStr Immunohistochemical evaluation of angiogenesis markers VEGF and Angipoietin-2 in Hepatocellular Carcinoma and precursor lesions of cirrhotic explants
title_full_unstemmed Immunohistochemical evaluation of angiogenesis markers VEGF and Angipoietin-2 in Hepatocellular Carcinoma and precursor lesions of cirrhotic explants
title_sort Immunohistochemical evaluation of angiogenesis markers VEGF and Angipoietin-2 in Hepatocellular Carcinoma and precursor lesions of cirrhotic explants
author Andrà Costa Teixeira
author_facet Andrà Costa Teixeira
author_role author
dc.contributor.advisor1.fl_str_mv Fabio Rocha Fernandes TÃvora
dc.contributor.advisor1ID.fl_str_mv 80063829304
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/5995375126302920
dc.contributor.referee1.fl_str_mv Paulo Roberto Carvalho de Almeida
dc.contributor.referee1ID.fl_str_mv 11969130300
dc.contributor.referee1Lattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4702849Y9
dc.contributor.referee2.fl_str_mv Ivelise Regina Canito Brasil
dc.contributor.referee2ID.fl_str_mv 30931339391
dc.contributor.referee2Lattes.fl_str_mv Ivelise Regina Canito Brasil
dc.contributor.referee3.fl_str_mv Josà Telmo ValenÃa JÃnior
dc.contributor.referee3ID.fl_str_mv 43839240344
dc.contributor.authorID.fl_str_mv 06188030684
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/6115237686268421
dc.contributor.author.fl_str_mv Andrà Costa Teixeira
contributor_str_mv Fabio Rocha Fernandes TÃvora
Paulo Roberto Carvalho de Almeida
Ivelise Regina Canito Brasil
Josà Telmo ValenÃa JÃnior
dc.subject.cnpq.fl_str_mv ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
topic ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
dc.description.abstract.por.fl_txt_mv Hepatocellular carcinoma (HCC) is a global health problem and is associated with chronic liver disease, especially in the cirrhotic phase. This tumor can be preceded by precursor lesions, namely low and high grade dysplastic nodules, and regenerative nodules, typical of cirrhosis. The current study evaluated the immunohistochemical expression of VEGF and angiopoietin-2 in HCC and precursor lesions is a single institution series of liver explants between 2013-2015 using tissue microarray methods. Immunohistochemical variables were correlated with angiogenesis and prognostic parameters. 107 nodules from 67 patients were studied, including 26 HCC and 5 dysplastic nodules. There was no significant epidemiologic difference between HCC, dysplastic nodules and regenerative nodule groups. Angiopoietin-2 was significantly more expressed in HCC nodules when compared with regenerative lesions (p < 0,0001*). VEGF and Ang-2 expression correlated with each other (p=0,006) and with number of unpaired arteries within nodules (p=0,03 â VEGF) and with the percentage of CD34 positive sinusoids (p < 0,0001 â VEGF and p< 0,007 â Ang-2). There was no significant correlation between any of the immunohistochemical parameters with clinical staging, number of gross lesions and histologic grade in cases of HCC. Angiopoietin-2 had a sensitivity of 54% and 96,25% of specificity for HCC diagnosis, and VEGF had a sensitivity of 69,23% and specificity of 31,25%. Our study shows that Ang-2 may be a good marker for HCC diagnosis when compared to others that are routinely used for this purpose. VEGF is not a good marker due to its lack of specificity, although other studies showed that it may be associated with prognostic parameters. Finally, our data reinforce the importance of angiogenesis evalutation in the development of HCC and its potential applicability as a diagnostic tool.
O carcinoma hepatocelular (CHC) constitui um problema de saÃde global e està relacionado a hepatopatias crÃnicas em fase de cirrose. Esta neoplasia à geralmente precedida por lesÃes precursoras denominadas nÃdulos displÃsicos de baixo grau (LGDN) e alto grau (HGDN), os quais por sua vez sÃo provenientes dos nÃdulos regenerativos (NR) tÃpicos da cirrose. Este trabalho avaliou a expressÃo imuno-histoquÃmica dos marcadores VEGF e Angiopoietina-2 no CHC e nas lesÃes precursoras de explantes de pacientes cirrÃticos transplantados no Hospital Geral de Fortaleza nos anos de 2013 a 2015, correlacionando esta expressÃo a outros parÃmetros de angiogÃnese e prognÃsticos. Foram incluÃdos no estudo 107 nÃdulos de 67 pacientes com CHC e/ou lesÃes precursoras para confecÃÃo de âtissue microarrayâ (TMA). NÃo houve diferenÃas demogrÃficas entre os pacientes com CHC e nÃdulos displÃsicos ou regenerativos. O marcador Angiopoietina-2 apresentou diferenÃa de imunoexpressÃo entre as classes de nÃdulos (p < 0,0001*), sendo maior nos pacientes com CHC. Os marcadores VEGF e Angiopoietina-2 mostraram correlaÃÃo significativa entre si (&#961;=0,006) e com outros parÃmetros, tais como nÃmero de artÃrias (p=0,03 para VEGF) e positividade à imuno-histoquÃmica para CD34 (p < 0,0001 para VEGF e p = 0,007 para Ang-2). NÃo houve associaÃÃo entre os marcadores avaliados e parÃmetros utilizados para determinaÃÃo de estadiamento e prognÃstico do CHC, tais como tamanho, nÃmero de lesÃes no explante e grau histolÃgico. A Angiopoietina-2 apresentou sensibilidade de 54% e especificidade de 96,25% para o diagnÃstico de malignidade, enquanto o VEGF apresentou sensibilidade de 69,23% e especificidade de 31,25%. Nosso estudo mostrou que a angiopoietina-2 representa um bom marcador para o diagnÃstico do CHC quando comparado aos que sÃo utilizados atualmente, enquanto o VEGF, embora tenha apresentado correlaÃÃo com parÃmetros prognÃsticos em outros estudos, nÃo se mostra um bom marcador por sua baixa especificidade. Por fim, os dados reforÃam a importÃncia de melhor avaliaÃÃo da angiogÃnese no desenvolvimento do CHC e seu papel no diagnÃstico anatomopatolÃgico destas lesÃes.
description Hepatocellular carcinoma (HCC) is a global health problem and is associated with chronic liver disease, especially in the cirrhotic phase. This tumor can be preceded by precursor lesions, namely low and high grade dysplastic nodules, and regenerative nodules, typical of cirrhosis. The current study evaluated the immunohistochemical expression of VEGF and angiopoietin-2 in HCC and precursor lesions is a single institution series of liver explants between 2013-2015 using tissue microarray methods. Immunohistochemical variables were correlated with angiogenesis and prognostic parameters. 107 nodules from 67 patients were studied, including 26 HCC and 5 dysplastic nodules. There was no significant epidemiologic difference between HCC, dysplastic nodules and regenerative nodule groups. Angiopoietin-2 was significantly more expressed in HCC nodules when compared with regenerative lesions (p < 0,0001*). VEGF and Ang-2 expression correlated with each other (p=0,006) and with number of unpaired arteries within nodules (p=0,03 â VEGF) and with the percentage of CD34 positive sinusoids (p < 0,0001 â VEGF and p< 0,007 â Ang-2). There was no significant correlation between any of the immunohistochemical parameters with clinical staging, number of gross lesions and histologic grade in cases of HCC. Angiopoietin-2 had a sensitivity of 54% and 96,25% of specificity for HCC diagnosis, and VEGF had a sensitivity of 69,23% and specificity of 31,25%. Our study shows that Ang-2 may be a good marker for HCC diagnosis when compared to others that are routinely used for this purpose. VEGF is not a good marker due to its lack of specificity, although other studies showed that it may be associated with prognostic parameters. Finally, our data reinforce the importance of angiogenesis evalutation in the development of HCC and its potential applicability as a diagnostic tool.
publishDate 2016
dc.date.issued.fl_str_mv 2016-02-24
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
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dc.publisher.none.fl_str_mv Universidade Federal do CearÃ
dc.publisher.program.fl_str_mv Programa de PÃs-GraduaÃÃo em Patologia
dc.publisher.initials.fl_str_mv UFC
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publisher.none.fl_str_mv Universidade Federal do CearÃ
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da UFC
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