Relação entre a presença de macrófagos no microambiente tumoral e fatores prognósticos em câncer de mama

Detalhes bibliográficos
Ano de defesa: 2018
Autor(a) principal: Labre, Luciana Vieira Queiroz lattes
Orientador(a): Santos, Silvia Helena Rabelo dos lattes
Banca de defesa: Santos, Silvia Helena Rabelo, Freitas Júnior, Ruffo de, Batista, Aline Carvalho, Celes, Mara Rúbia Nunes, Costa, Nádia do Lago
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 Medicina Tropical e Saúde Publica (IPTSP)
Departamento: Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG)
País: Brasil
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tede/9706
Resumo: Introduction: The analysis of possible biomarkers associated with the more aggressive behavior of breast carcinomas, linked to clinical and prognostic information, can provide important data in the treatment of patients with breast cancer. There are indications that the presence of tumor associated macrophages (TAMs) in the tumor microenvironment is associated with a worse prognosis for women with breast cancer. Objective: To evaluate the importance of the presence of macrophages in the tumor microenvironment in breast neoplasms. Methods: This retrospective cross-sectional study included 93 cases of women with invasive ductal breast cancer and submitted to immunohistochemical analysis of the markers for CD68 (M1 / M2) and CD163 (M2) macrophages. The counts of CD68 + and CD163 + cells were performed in a peritumoral region, considering hot spot fields, and the cases under study were classified as low infiltration or high infiltration using semiquantitative evaluation of cell marking. Statistical analysis was performed using the Stata 13.0 program (Stata Corp., College Station, TX, United States), with bivariate analysis, considering the level of significance of p <0.05, and multivariate analysis where the variables with p <0.2 were submitted to the logistic regression test. The Kaplan-Meier method and the log-rank test were used in the analysis of survival curves. Results: High levels of TAMs (CD68 +) were significantly correlated with: patient age, presence of distant metastasis, more advanced tumor staging, absence of estrogen receptors (ER) and progesterone (PR), and triple negative breast cancer (TN). The reduction of the overall survival rate in the cases of women with breast cancer studied was significantly associated with high infiltration of TAMs (CD68 +). The high infiltration of TAMs phenotype M2 (CD163 +) was significantly correlated with the independent variables presence of distant metastasis, absence of RE and TN breast cancer. Conclusions: The association of the analysis of TAM biomarkers with clinical and prognostic information showed that the high presence of macrophagic infiltrate has a significant prognostic value, adding information on the relationship between the presence of macrophages in the tumor microenvironment of cases of women with carcinoma and the clinical-pathological characteristics of the tumor. In addition, TAMs appear as potential prognostic markers for breast cancer.
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spelling Santos, Silvia Helena Rabelo doshttp://lattes.cnpq.br/4994826511439492Saddi, Vera Aparecidahttp://lattes.cnpq.br/7496804650895441Santos, Silvia Helena RabeloFreitas Júnior, Ruffo deBatista, Aline CarvalhoCeles, Mara Rúbia NunesCosta, Nádia do Lagohttp://lattes.cnpq.br/2732333433582512Labre, Luciana Vieira Queiroz2019-06-13T13:26:28Z2018-04-26LABRE, Luciana Vieira Queiroz. Relação entre a presença de macrófagos no microambiente tumoral e fatores prognósticos em câncer de mama. 2018. 121 f. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2018.http://repositorio.bc.ufg.br/tede/handle/tede/9706Introduction: The analysis of possible biomarkers associated with the more aggressive behavior of breast carcinomas, linked to clinical and prognostic information, can provide important data in the treatment of patients with breast cancer. There are indications that the presence of tumor associated macrophages (TAMs) in the tumor microenvironment is associated with a worse prognosis for women with breast cancer. Objective: To evaluate the importance of the presence of macrophages in the tumor microenvironment in breast neoplasms. Methods: This retrospective cross-sectional study included 93 cases of women with invasive ductal breast cancer and submitted to immunohistochemical analysis of the markers for CD68 (M1 / M2) and CD163 (M2) macrophages. The counts of CD68 + and CD163 + cells were performed in a peritumoral region, considering hot spot fields, and the cases under study were classified as low infiltration or high infiltration using semiquantitative evaluation of cell marking. Statistical analysis was performed using the Stata 13.0 program (Stata Corp., College Station, TX, United States), with bivariate analysis, considering the level of significance of p <0.05, and multivariate analysis where the variables with p <0.2 were submitted to the logistic regression test. The Kaplan-Meier method and the log-rank test were used in the analysis of survival curves. Results: High levels of TAMs (CD68 +) were significantly correlated with: patient age, presence of distant metastasis, more advanced tumor staging, absence of estrogen receptors (ER) and progesterone (PR), and triple negative breast cancer (TN). The reduction of the overall survival rate in the cases of women with breast cancer studied was significantly associated with high infiltration of TAMs (CD68 +). The high infiltration of TAMs phenotype M2 (CD163 +) was significantly correlated with the independent variables presence of distant metastasis, absence of RE and TN breast cancer. Conclusions: The association of the analysis of TAM biomarkers with clinical and prognostic information showed that the high presence of macrophagic infiltrate has a significant prognostic value, adding information on the relationship between the presence of macrophages in the tumor microenvironment of cases of women with carcinoma and the clinical-pathological characteristics of the tumor. In addition, TAMs appear as potential prognostic markers for breast cancer.Introdução: A análise de possíveis biomarcadores associados ao comportamento mais agressivo dos carcinomas de mama, vinculada a informações clínicas e de prognóstico, pode fornecer dados importantes na abordagem de pacientes com câncer de mama. Há indicações de que a presença de macrófagos associados a tumor (TAMs) no microambiente tumoral esteja associada a pior prognóstico para mulheres com câncer de mama. Objetivo: Avaliar a importância da presença de macrófagos no microambiente tumoral em neoplasias de mama. Métodos: Este estudo de corte transversal retrospectivo incluiu 93 casos de mulheres com câncer de mama ductal invasivo e submetidos a análise imuno-histoquímica dos marcadores para macrófagos CD68 (M1/M2) e CD163 (M2). A contagem de células marcadas com CD68+ e CD163+ foi realizada em região peritumoral, considerando campos hot spot, e os casos em estudo foram classificados em de baixa infiltração ou alta infiltração utilizando avaliação semiquantitativa de marcação celular. Para a realização das análises estatísticas, foi utilizado o programa Stata 13.0 (Stata Corp., College Station, TX, Estados Unidos), com analises bivariada, considerando o nível de significância de p < 0,05, e multivariada onde as variáveis com p < 0,2 foram submetidas ao teste de regressão logística. O método de Kaplan-Meier e o teste de log-rank foram utilizados na análise das curvas de sobrevida. Resultados: Níveis elevados de TAMs (CD68+) correlacionaram-se significativamente com: idade das pacientes, presença de metástase à distância, estadiamento tumoral mais avançado, ausência de receptores de estrógeno (RE) e progesterona (RP) e câncer de mama triplo negativo (TN). A redução da taxa global de sobrevida nos casos de mulheres com câncer de mama estudados foi significativamente associada com alta infiltração de TAMs (CD68+). A alta infiltração de TAMs fenótipo M2 (CD163+) foi significativamente correlacionada com as variáveis independentes presença de metástase à distância, ausência de RE e câncer de mama TN. Conclusões: A associação da análise de biomarcadores TAMs com a obtenção de informações clínicas e de prognóstico mostrou que a presença elevada de infiltrado macrofagico tem valor prognóstico significativo, agregando informações sobre a relação entre a presença de macrófagos no microambiente tumoral de casos de mulheres com carcinoma de mama e as características clínico-patológicas do tumor. Em adição a isso, os TAMs despontam como possíveis marcadores prognósticos para o câncer de mama.Submitted by Marlene Santos (marlene.bc.ufg@gmail.com) on 2019-06-12T18:47:11Z No. of bitstreams: 2 Tese - Luciana Vieira Queiroz Labre - 2018.pdf: 5717675 bytes, checksum: b2ac341f86fb0b887224b9ea996ca465 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2019-06-13T13:26:28Z (GMT) No. of bitstreams: 2 Tese - Luciana Vieira Queiroz Labre - 2018.pdf: 5717675 bytes, checksum: b2ac341f86fb0b887224b9ea996ca465 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5)Made available in DSpace on 2019-06-13T13:26:28Z (GMT). No. of bitstreams: 2 Tese - Luciana Vieira Queiroz Labre - 2018.pdf: 5717675 bytes, checksum: b2ac341f86fb0b887224b9ea996ca465 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2018-04-26Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfporUniversidade Federal de GoiásPrograma de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP)UFGBrasilInstituto de Patologia Tropical e Saúde Pública - IPTSP (RG)http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessCâncer de mamaMacrófagosBiomarcadoresFatores prognósticosBreast cancerMacrophagesBiomarkersPrognostic factorsSAUDE COLETIVA::SAUDE PUBLICARelação entre a presença de macrófagos no microambiente tumoral e fatores prognósticos em câncer de mamaRelationship between the presence of macrophages in the tumor microenvironment and prognostic factors in breast cancerinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis6085308344741430434600600600600-776901144456455628831126492445846009792075167498588264571reponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGLICENSElicense.txtlicense.txttext/plain; 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dc.title.eng.fl_str_mv Relação entre a presença de macrófagos no microambiente tumoral e fatores prognósticos em câncer de mama
dc.title.alternative.eng.fl_str_mv Relationship between the presence of macrophages in the tumor microenvironment and prognostic factors in breast cancer
title Relação entre a presença de macrófagos no microambiente tumoral e fatores prognósticos em câncer de mama
spellingShingle Relação entre a presença de macrófagos no microambiente tumoral e fatores prognósticos em câncer de mama
Labre, Luciana Vieira Queiroz
Câncer de mama
Macrófagos
Biomarcadores
Fatores prognósticos
Breast cancer
Macrophages
Biomarkers
Prognostic factors
SAUDE COLETIVA::SAUDE PUBLICA
title_short Relação entre a presença de macrófagos no microambiente tumoral e fatores prognósticos em câncer de mama
title_full Relação entre a presença de macrófagos no microambiente tumoral e fatores prognósticos em câncer de mama
title_fullStr Relação entre a presença de macrófagos no microambiente tumoral e fatores prognósticos em câncer de mama
title_full_unstemmed Relação entre a presença de macrófagos no microambiente tumoral e fatores prognósticos em câncer de mama
title_sort Relação entre a presença de macrófagos no microambiente tumoral e fatores prognósticos em câncer de mama
author Labre, Luciana Vieira Queiroz
author_facet Labre, Luciana Vieira Queiroz
author_role author
dc.contributor.advisor1.fl_str_mv Santos, Silvia Helena Rabelo dos
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/4994826511439492
dc.contributor.advisor-co1.fl_str_mv Saddi, Vera Aparecida
dc.contributor.advisor-co1Lattes.fl_str_mv http://lattes.cnpq.br/7496804650895441
dc.contributor.referee1.fl_str_mv Santos, Silvia Helena Rabelo
dc.contributor.referee2.fl_str_mv Freitas Júnior, Ruffo de
dc.contributor.referee3.fl_str_mv Batista, Aline Carvalho
dc.contributor.referee4.fl_str_mv Celes, Mara Rúbia Nunes
dc.contributor.referee5.fl_str_mv Costa, Nádia do Lago
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/2732333433582512
dc.contributor.author.fl_str_mv Labre, Luciana Vieira Queiroz
contributor_str_mv Santos, Silvia Helena Rabelo dos
Saddi, Vera Aparecida
Santos, Silvia Helena Rabelo
Freitas Júnior, Ruffo de
Batista, Aline Carvalho
Celes, Mara Rúbia Nunes
Costa, Nádia do Lago
dc.subject.por.fl_str_mv Câncer de mama
Macrófagos
Biomarcadores
Fatores prognósticos
topic Câncer de mama
Macrófagos
Biomarcadores
Fatores prognósticos
Breast cancer
Macrophages
Biomarkers
Prognostic factors
SAUDE COLETIVA::SAUDE PUBLICA
dc.subject.eng.fl_str_mv Breast cancer
Macrophages
Biomarkers
Prognostic factors
dc.subject.cnpq.fl_str_mv SAUDE COLETIVA::SAUDE PUBLICA
description Introduction: The analysis of possible biomarkers associated with the more aggressive behavior of breast carcinomas, linked to clinical and prognostic information, can provide important data in the treatment of patients with breast cancer. There are indications that the presence of tumor associated macrophages (TAMs) in the tumor microenvironment is associated with a worse prognosis for women with breast cancer. Objective: To evaluate the importance of the presence of macrophages in the tumor microenvironment in breast neoplasms. Methods: This retrospective cross-sectional study included 93 cases of women with invasive ductal breast cancer and submitted to immunohistochemical analysis of the markers for CD68 (M1 / M2) and CD163 (M2) macrophages. The counts of CD68 + and CD163 + cells were performed in a peritumoral region, considering hot spot fields, and the cases under study were classified as low infiltration or high infiltration using semiquantitative evaluation of cell marking. Statistical analysis was performed using the Stata 13.0 program (Stata Corp., College Station, TX, United States), with bivariate analysis, considering the level of significance of p <0.05, and multivariate analysis where the variables with p <0.2 were submitted to the logistic regression test. The Kaplan-Meier method and the log-rank test were used in the analysis of survival curves. Results: High levels of TAMs (CD68 +) were significantly correlated with: patient age, presence of distant metastasis, more advanced tumor staging, absence of estrogen receptors (ER) and progesterone (PR), and triple negative breast cancer (TN). The reduction of the overall survival rate in the cases of women with breast cancer studied was significantly associated with high infiltration of TAMs (CD68 +). The high infiltration of TAMs phenotype M2 (CD163 +) was significantly correlated with the independent variables presence of distant metastasis, absence of RE and TN breast cancer. Conclusions: The association of the analysis of TAM biomarkers with clinical and prognostic information showed that the high presence of macrophagic infiltrate has a significant prognostic value, adding information on the relationship between the presence of macrophages in the tumor microenvironment of cases of women with carcinoma and the clinical-pathological characteristics of the tumor. In addition, TAMs appear as potential prognostic markers for breast cancer.
publishDate 2018
dc.date.issued.fl_str_mv 2018-04-26
dc.date.accessioned.fl_str_mv 2019-06-13T13:26:28Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
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dc.identifier.citation.fl_str_mv LABRE, Luciana Vieira Queiroz. Relação entre a presença de macrófagos no microambiente tumoral e fatores prognósticos em câncer de mama. 2018. 121 f. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2018.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tede/9706
identifier_str_mv LABRE, Luciana Vieira Queiroz. Relação entre a presença de macrófagos no microambiente tumoral e fatores prognósticos em câncer de mama. 2018. 121 f. Tese (Doutorado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2018.
url http://repositorio.bc.ufg.br/tede/handle/tede/9706
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language por
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dc.publisher.none.fl_str_mv Universidade Federal de Goiás
dc.publisher.program.fl_str_mv Programa de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP)
dc.publisher.initials.fl_str_mv UFG
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG)
publisher.none.fl_str_mv Universidade Federal de Goiás
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collection Repositório Institucional da UFG
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http://repositorio.bc.ufg.br/tede/bitstreams/d28bff1d-3839-4026-bbed-a3f4177ae2a5/download
http://repositorio.bc.ufg.br/tede/bitstreams/41aa82d6-dcfb-4461-8da5-f52629ca2d0d/download
bitstream.checksum.fl_str_mv bd3efa91386c1718a7f26a329fdcb468
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bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositório Institucional da UFG - Universidade Federal de Goiás (UFG)
repository.mail.fl_str_mv tasesdissertacoes.bc@ufg.br
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