Expressão nuclear de IGF-1R (insulin-like growth factor-1 receptor) e sua associação com parâmetros clínico-patológicos e desfechos clínicos em portadores de carcinoma hepatocelular
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | http://hdl.handle.net/1843/55344 |
Resumo: | Introduction: hepatocellular carcinoma (HCC), the most common primary tumor of the liver, ranks as the sixth most commonly diagnosed malignancy and the third leading cause of cancer deaths in the world. Despite the therapeutic advances, the prognosis remains poor, which reflects the need to better understand the complex mechanisms involved in the carcinogenesis of this neoplasm. IGF-1R (Insulin-like Growth Factor-1 Receptor) is a transmembrane receptor with tyrosine kinase domains, which acts, together with its ligands, in physiological growth as well as in pathological processes. In hepatocarcinogenesis, IGF- 1R activation can trigger intracellular signaling cascades, which lead to events necessary for the initiation, promotion and development of cancer. Current evidence points to another characteristic of IGF-1R, which stands it out among other receptors: its ability to translocate to the nucleus, which could allow the modulation of growth events at a level of genomic control, contributing to neoplastic transformation. Clarifying the role of IGF-1R in HCC may contribute to a better understanding of this complex disease. Objective: this study aims to evaluate the nuclear expression of IGF-1R in samples of hepatocellular carcinoma submitted to liver transplantation or partial liver resection, and to investigate its association with clinicopathological parameters and clinical outcomes. Methodology: an immunohistochemical evaluation of the nuclear expression of IGF-1R was performed in samples from liver explants or partial surgical resections, between the years 2000 to 2020, for the treatment of HCC at the Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG). Medical records were reviewed to collect clinical data and specimen slides were reviewed to collect pathological data. Results: of the patients included in the study (n=111), the main etiologies of the chronic liver disease were hepatitis C virus (44.1%), hepatitis B virus (16.2%), ethanolic (16.2%) %) and cryptogenic (17.1%). IGF-1R expression was demonstrated in the nucleus of tumor cells and in the adjacent cirrhotic parenchyma. In univariate analysis, a higher nuclear expression of IGF-1R was observed in HCC than in cirrhosis (p < 0.001). and in moderately/poorly differentiated tumors (p < 0.001), a higher nuclear expression was also demonstrated, in cirrhosis, in cases of hepatitis B (p = 0.002). In the multivariate model, higher nuclear expression of IGF-1R was observed in the tumor than in cirrhosis (p<0.001) and higher nuclear expression in tumors classified as moderately/poorly differentiated (p<0.001). However, no statistically significant association was observed between the presence of immunoexpression and cases of cirrhosis caused by HBV (p=0.999). No association was observed between clinical outcomes and other variables with the nuclear expression of IGF-1R in the tumor or in the area of cirrhosis (p > 0.05). Discussion: data show greater nuclear expression of IGF-1R in HCC than in adjacent cirrhotic parenchyma, suggesting that its translocation may be one of the initial events in hepatocarcinogenesis. Despite the lack of association with long-term clinical outcomes, receptor expression is independently associated with the degree of differentiation, which is a histopathological parameter of poor prognosis. However, further studies are needed to further assess the association with different etiologies, given the heterogeneity of the disease. |
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Expressão nuclear de IGF-1R (insulin-like growth factor-1 receptor) e sua associação com parâmetros clínico-patológicos e desfechos clínicos em portadores de carcinoma hepatocelularNuclear expression of IGF-1R (insulin-like growth factor receptor 1) and its association with clinical-pathological parameters and clinical outcomes in patients with hepatocellular carcinomaIgf-1rCarcinoma hepatocelularTranslocação nuclearCirrose hepática.Receptor IGF Tipo 1Carcinoma HepatocelularCirrose HepáticaDissertação AcadêmicaIntroduction: hepatocellular carcinoma (HCC), the most common primary tumor of the liver, ranks as the sixth most commonly diagnosed malignancy and the third leading cause of cancer deaths in the world. Despite the therapeutic advances, the prognosis remains poor, which reflects the need to better understand the complex mechanisms involved in the carcinogenesis of this neoplasm. IGF-1R (Insulin-like Growth Factor-1 Receptor) is a transmembrane receptor with tyrosine kinase domains, which acts, together with its ligands, in physiological growth as well as in pathological processes. In hepatocarcinogenesis, IGF- 1R activation can trigger intracellular signaling cascades, which lead to events necessary for the initiation, promotion and development of cancer. Current evidence points to another characteristic of IGF-1R, which stands it out among other receptors: its ability to translocate to the nucleus, which could allow the modulation of growth events at a level of genomic control, contributing to neoplastic transformation. Clarifying the role of IGF-1R in HCC may contribute to a better understanding of this complex disease. Objective: this study aims to evaluate the nuclear expression of IGF-1R in samples of hepatocellular carcinoma submitted to liver transplantation or partial liver resection, and to investigate its association with clinicopathological parameters and clinical outcomes. Methodology: an immunohistochemical evaluation of the nuclear expression of IGF-1R was performed in samples from liver explants or partial surgical resections, between the years 2000 to 2020, for the treatment of HCC at the Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG). Medical records were reviewed to collect clinical data and specimen slides were reviewed to collect pathological data. Results: of the patients included in the study (n=111), the main etiologies of the chronic liver disease were hepatitis C virus (44.1%), hepatitis B virus (16.2%), ethanolic (16.2%) %) and cryptogenic (17.1%). IGF-1R expression was demonstrated in the nucleus of tumor cells and in the adjacent cirrhotic parenchyma. In univariate analysis, a higher nuclear expression of IGF-1R was observed in HCC than in cirrhosis (p < 0.001). and in moderately/poorly differentiated tumors (p < 0.001), a higher nuclear expression was also demonstrated, in cirrhosis, in cases of hepatitis B (p = 0.002). In the multivariate model, higher nuclear expression of IGF-1R was observed in the tumor than in cirrhosis (p<0.001) and higher nuclear expression in tumors classified as moderately/poorly differentiated (p<0.001). However, no statistically significant association was observed between the presence of immunoexpression and cases of cirrhosis caused by HBV (p=0.999). No association was observed between clinical outcomes and other variables with the nuclear expression of IGF-1R in the tumor or in the area of cirrhosis (p > 0.05). Discussion: data show greater nuclear expression of IGF-1R in HCC than in adjacent cirrhotic parenchyma, suggesting that its translocation may be one of the initial events in hepatocarcinogenesis. Despite the lack of association with long-term clinical outcomes, receptor expression is independently associated with the degree of differentiation, which is a histopathological parameter of poor prognosis. However, further studies are needed to further assess the association with different etiologies, given the heterogeneity of the disease.Introdução: o carcinoma hepatocelular (CHC), tumor primário mais comum do fígado, representa a sexta neoplasia maligna mais diagnosticada e a terceira maior causa de morte por câncer no mundo. Apesar dos avanços terapêuticos, o prognóstico ainda permanece sombrio, o que reflete a necessidade de se entender melhor os complexos mecanismos envolvidos na carcinogênese dessa neoplasia. O IGF-1R (Insulin-like Growth Factor-1 Receptor) é um receptor transmembrana com domínios de tirosina-quinase, que atua, em conjunto com seus ligantes, no crescimento fisiológico, bem como em processos patológicos. Na hepatocarcinogênese, a ativação do IGF-1R pode deflagrar cascatas de sinalização intracelular, que levam a eventos necessários para a iniciação, promoção e desenvolvimento do câncer. Evidências atuais apontam outra característica do IGF-1R, que o destaca em relação a outros receptores: sua capacidade de se translocar para o núcleo, o que poderia permitir a modulação de eventos de crescimento em um nível de controle genômico, contribuindo assim para transformação neoplásica. O esclarecimento acerca do papel do IGF-1R no CHC poderá contribuir para melhor entendimento dessa doença tão complexa. Objetivo: esse estudo visa avaliar a expressão nuclear de IGF-1R em amostras de carcinoma hepatocelular submetidos a transplante hepático ou ressecção hepática parcial, e investigar sua associação com parâmetros clinicopatologicos e com desfechos clínicos. Metodologia: foi realizada avaliação imuno- histoquímica da expressão nuclear de IGF-1R em amostras provenientes de explantes hepáticos ou ressecções cirúrgicas parciais, entre os anos de 2000 à 2020, para o tratamento de CHC no Hospital das Clínicas da Universidade Federal de Minas Gerais (HC- UFMG). Os prontuários médicos dos pacientes foram revisados para coletar dados clínicos e as lâminas das amostras foram revisadas para coletar dados anatomopatológicos. Resultados: dos pacientes incluídos no estudo (n=111), as principias etiologias da hepatopatia crônica de base foram o vírus da hepatite C (44,1%), vírus da hepatite B (16,2%), etanólica (16,2%) e criptogênica (17,1%). Foi demostrada expressão de IGF-1R no núcleo de células tumorais no CHC e no parênquima cirrótico adjacente. Na análise univariada, foi observada uma maior expressão nuclear de IGF- 1R no CHC do que na cirrose (p < 0,001) e em tumores moderadamente/pouco diferenciados (p < 0,001).Também foi demonstrada uma maior expressão nuclear, na cirrose, em casos de hepatite B (p = 0,002). No modelo multivariado, foi observada maior expressão nuclear de IGF- 1R no tumor do que na cirrose (p< 0,001) e maior expressão nuclear em tumores classificados como moderadamente/pouco diferenciados (p< 0,001). Entretanto, não foi observada associação estatisticamente significativa entre a imunoexpressão e os casos de cirrose causados pelo HBV (p=0,999). Não foi observada associação entre os desfechos clínicos e as demais variáveis com a expressão nuclear de IGF-1R no tumor ou na área de cirrose (p > 0,05). Discussão: os dados mostram maior expressão nuclear de IGF-1R no HCC do que no parênquima cirrótico adjacente, sugerindo que a sua translocação possa ser um dos eventos iniciais na hepatocarcinogênese. Apesar da ausência de associação com desfechos clínicos a longo prazo, a expressão do receptor se associa independentemente com o grau de diferenciação, que é um parâmetro histopatológico de mau prognóstico. Entretanto, mais estudos são necessários, inclusive para avaliação da associação com diferentes etiologias, tendo em vista a heterogeneidade da doença.Universidade Federal de Minas GeraisBrasilICB - DEPARTAMENTO DE PATOLOGIAPrograma de Pós-Graduação em PatologiaUFMGPaula Vieira Teixeira Vidigalhttp://lattes.cnpq.br/8537115801581858Paulo Henrique Costa DinizMaria Luiza Peloso Maia2023-06-26T15:13:01Z2023-06-26T15:13:01Z2022-08-26info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://hdl.handle.net/1843/55344porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMG2023-06-26T15:13:01Zoai:repositorio.ufmg.br:1843/55344Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2023-06-26T15:13:01Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.none.fl_str_mv |
Expressão nuclear de IGF-1R (insulin-like growth factor-1 receptor) e sua associação com parâmetros clínico-patológicos e desfechos clínicos em portadores de carcinoma hepatocelular Nuclear expression of IGF-1R (insulin-like growth factor receptor 1) and its association with clinical-pathological parameters and clinical outcomes in patients with hepatocellular carcinoma |
title |
Expressão nuclear de IGF-1R (insulin-like growth factor-1 receptor) e sua associação com parâmetros clínico-patológicos e desfechos clínicos em portadores de carcinoma hepatocelular |
spellingShingle |
Expressão nuclear de IGF-1R (insulin-like growth factor-1 receptor) e sua associação com parâmetros clínico-patológicos e desfechos clínicos em portadores de carcinoma hepatocelular Maria Luiza Peloso Maia Igf-1r Carcinoma hepatocelular Translocação nuclear Cirrose hepática. Receptor IGF Tipo 1 Carcinoma Hepatocelular Cirrose Hepática Dissertação Acadêmica |
title_short |
Expressão nuclear de IGF-1R (insulin-like growth factor-1 receptor) e sua associação com parâmetros clínico-patológicos e desfechos clínicos em portadores de carcinoma hepatocelular |
title_full |
Expressão nuclear de IGF-1R (insulin-like growth factor-1 receptor) e sua associação com parâmetros clínico-patológicos e desfechos clínicos em portadores de carcinoma hepatocelular |
title_fullStr |
Expressão nuclear de IGF-1R (insulin-like growth factor-1 receptor) e sua associação com parâmetros clínico-patológicos e desfechos clínicos em portadores de carcinoma hepatocelular |
title_full_unstemmed |
Expressão nuclear de IGF-1R (insulin-like growth factor-1 receptor) e sua associação com parâmetros clínico-patológicos e desfechos clínicos em portadores de carcinoma hepatocelular |
title_sort |
Expressão nuclear de IGF-1R (insulin-like growth factor-1 receptor) e sua associação com parâmetros clínico-patológicos e desfechos clínicos em portadores de carcinoma hepatocelular |
author |
Maria Luiza Peloso Maia |
author_facet |
Maria Luiza Peloso Maia |
author_role |
author |
dc.contributor.none.fl_str_mv |
Paula Vieira Teixeira Vidigal http://lattes.cnpq.br/8537115801581858 Paulo Henrique Costa Diniz |
dc.contributor.author.fl_str_mv |
Maria Luiza Peloso Maia |
dc.subject.por.fl_str_mv |
Igf-1r Carcinoma hepatocelular Translocação nuclear Cirrose hepática. Receptor IGF Tipo 1 Carcinoma Hepatocelular Cirrose Hepática Dissertação Acadêmica |
topic |
Igf-1r Carcinoma hepatocelular Translocação nuclear Cirrose hepática. Receptor IGF Tipo 1 Carcinoma Hepatocelular Cirrose Hepática Dissertação Acadêmica |
description |
Introduction: hepatocellular carcinoma (HCC), the most common primary tumor of the liver, ranks as the sixth most commonly diagnosed malignancy and the third leading cause of cancer deaths in the world. Despite the therapeutic advances, the prognosis remains poor, which reflects the need to better understand the complex mechanisms involved in the carcinogenesis of this neoplasm. IGF-1R (Insulin-like Growth Factor-1 Receptor) is a transmembrane receptor with tyrosine kinase domains, which acts, together with its ligands, in physiological growth as well as in pathological processes. In hepatocarcinogenesis, IGF- 1R activation can trigger intracellular signaling cascades, which lead to events necessary for the initiation, promotion and development of cancer. Current evidence points to another characteristic of IGF-1R, which stands it out among other receptors: its ability to translocate to the nucleus, which could allow the modulation of growth events at a level of genomic control, contributing to neoplastic transformation. Clarifying the role of IGF-1R in HCC may contribute to a better understanding of this complex disease. Objective: this study aims to evaluate the nuclear expression of IGF-1R in samples of hepatocellular carcinoma submitted to liver transplantation or partial liver resection, and to investigate its association with clinicopathological parameters and clinical outcomes. Methodology: an immunohistochemical evaluation of the nuclear expression of IGF-1R was performed in samples from liver explants or partial surgical resections, between the years 2000 to 2020, for the treatment of HCC at the Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG). Medical records were reviewed to collect clinical data and specimen slides were reviewed to collect pathological data. Results: of the patients included in the study (n=111), the main etiologies of the chronic liver disease were hepatitis C virus (44.1%), hepatitis B virus (16.2%), ethanolic (16.2%) %) and cryptogenic (17.1%). IGF-1R expression was demonstrated in the nucleus of tumor cells and in the adjacent cirrhotic parenchyma. In univariate analysis, a higher nuclear expression of IGF-1R was observed in HCC than in cirrhosis (p < 0.001). and in moderately/poorly differentiated tumors (p < 0.001), a higher nuclear expression was also demonstrated, in cirrhosis, in cases of hepatitis B (p = 0.002). In the multivariate model, higher nuclear expression of IGF-1R was observed in the tumor than in cirrhosis (p<0.001) and higher nuclear expression in tumors classified as moderately/poorly differentiated (p<0.001). However, no statistically significant association was observed between the presence of immunoexpression and cases of cirrhosis caused by HBV (p=0.999). No association was observed between clinical outcomes and other variables with the nuclear expression of IGF-1R in the tumor or in the area of cirrhosis (p > 0.05). Discussion: data show greater nuclear expression of IGF-1R in HCC than in adjacent cirrhotic parenchyma, suggesting that its translocation may be one of the initial events in hepatocarcinogenesis. Despite the lack of association with long-term clinical outcomes, receptor expression is independently associated with the degree of differentiation, which is a histopathological parameter of poor prognosis. However, further studies are needed to further assess the association with different etiologies, given the heterogeneity of the disease. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-08-26 2023-06-26T15:13:01Z 2023-06-26T15:13:01Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
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http://hdl.handle.net/1843/55344 |
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http://hdl.handle.net/1843/55344 |
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por |
language |
por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais Brasil ICB - DEPARTAMENTO DE PATOLOGIA Programa de Pós-Graduação em Patologia UFMG |
publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais Brasil ICB - DEPARTAMENTO DE PATOLOGIA Programa de Pós-Graduação em Patologia UFMG |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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Universidade Federal de Minas Gerais (UFMG) |
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UFMG |
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UFMG |
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Repositório Institucional da UFMG |
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Repositório Institucional da UFMG |
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Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG) |
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repositorio@ufmg.br |
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1816829677581369344 |