Valor prognóstico da expressão de HMGB1 e IL-33 em câncer de mama triplo negativo

Detalhes bibliográficos
Ano de defesa: 2023
Autor(a) principal: Sales, Francisca Janice Lopes
Orientador(a): Wong, Deysi Viviana Tenazoa
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufc.br/handle/riufc/74903
Resumo: Breast Cancer is one of the most frequent neoplasms worldwide, contributing to female morbidity and mortality. Triple Negative Breast Cancer (CMTN) is a highly aggressive subtype of cancer that is negative for estrogen and progesterone receptors and lacks overexpression of human epidermal growth factor type 2 (C-erbB2, HER2/neu). High Mobility Group 1 (HMGB1) is a DAMP (Damage Associated Molecular Pattern) that regulates tumorigenesis, proliferation, and malignant metastasis. IL-33, a cytokine related to cell damage, has been shown to play a role in tumorigenesis and tumor-associated inflammatory responses. This study aimed to analyze the expression of HMGB1 and IL-33 as prognostic factors for CMTN. Clinical-pathological data of 122 patients diagnosed with CMTN treated at Hospital Haroldo Juaçaba were evaluated. Additionally, a Tissue Microarray (TMA) block was constructed containing samples of paraffin blocks from the biopsies of 43 patients. Then, immunofluorescence for HMGB1 was performed to quantify the intensity of expression and the percentage of fluorescent cells with cytoplasmic (cHMGB1) staining. Immunohistochemistry for HMGB1 and IL-33 was performed using the Envision DAKO® Kit detection method. In the statistical analysis, significance was considered at p<0.05 using the statistical program SPSS v.17 and GraphPad Prism v.8. Analysis of clinicopathological data indicated that patients were over 40 years old (79%) and were diagnosed with grade 2-3 ductal carcinomas (96.3%). Tumor metastasis was observed in 1.9% of cases. 66.7% of patients with CMTN who underwent adjuvant chemotherapy had low expression of HMGB1 (p<0.05). Furthermore, it was found that of patients who relapsed, 77.8% of these had low cytoplasmic expression of HMGB1 compared to high expression (p<0.05). Overall survival was similar between patients with low versus high cytoplasmic HMGB1 expression (P=0.155). For IL-33, no significant results were found. However, we emphasize that the comparative graph between High and Low expression of IL-33 versus relapse showed that 19% of patients with IL-33 High expression had a disease relapse (p>0, 05). Thus, cytoplasmic HMGB1 expression was associated with relapse and adjuvant chemotherapy in CMTN patients.
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spelling Sales, Francisca Janice LopesWong, Deysi Viviana Tenazoa2023-11-07T16:27:07Z2023-11-07T16:27:07Z2023SALES, Francisca Janice Lopes. Valor prognóstico da expressão de HMGB1 e IL-33 em câncer. 2023. Dissertação (Mestrado em Patologia) – Centro de Ciências da Saúde, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://www.repositorio.ufc.br/handle/riufc/74903. Acesso em: 07 nov. 2023.http://repositorio.ufc.br/handle/riufc/74903Breast Cancer is one of the most frequent neoplasms worldwide, contributing to female morbidity and mortality. Triple Negative Breast Cancer (CMTN) is a highly aggressive subtype of cancer that is negative for estrogen and progesterone receptors and lacks overexpression of human epidermal growth factor type 2 (C-erbB2, HER2/neu). High Mobility Group 1 (HMGB1) is a DAMP (Damage Associated Molecular Pattern) that regulates tumorigenesis, proliferation, and malignant metastasis. IL-33, a cytokine related to cell damage, has been shown to play a role in tumorigenesis and tumor-associated inflammatory responses. This study aimed to analyze the expression of HMGB1 and IL-33 as prognostic factors for CMTN. Clinical-pathological data of 122 patients diagnosed with CMTN treated at Hospital Haroldo Juaçaba were evaluated. Additionally, a Tissue Microarray (TMA) block was constructed containing samples of paraffin blocks from the biopsies of 43 patients. Then, immunofluorescence for HMGB1 was performed to quantify the intensity of expression and the percentage of fluorescent cells with cytoplasmic (cHMGB1) staining. Immunohistochemistry for HMGB1 and IL-33 was performed using the Envision DAKO® Kit detection method. In the statistical analysis, significance was considered at p<0.05 using the statistical program SPSS v.17 and GraphPad Prism v.8. Analysis of clinicopathological data indicated that patients were over 40 years old (79%) and were diagnosed with grade 2-3 ductal carcinomas (96.3%). Tumor metastasis was observed in 1.9% of cases. 66.7% of patients with CMTN who underwent adjuvant chemotherapy had low expression of HMGB1 (p<0.05). Furthermore, it was found that of patients who relapsed, 77.8% of these had low cytoplasmic expression of HMGB1 compared to high expression (p<0.05). Overall survival was similar between patients with low versus high cytoplasmic HMGB1 expression (P=0.155). For IL-33, no significant results were found. However, we emphasize that the comparative graph between High and Low expression of IL-33 versus relapse showed that 19% of patients with IL-33 High expression had a disease relapse (p>0, 05). Thus, cytoplasmic HMGB1 expression was associated with relapse and adjuvant chemotherapy in CMTN patients.O Câncer de Mama é uma das neoplasias mais frequentes em todo o mundo, contribuindo para a morbimortalidade feminina. O Câncer de mama Triplo Negativo (CMTN) é um subtipo altamente agressivo de câncer que são negativos para os receptoresde estrógeno e progesterona, assim como não apresenta superexpressão do fator tipo 2 de crescimento epidérmico humano (C-erbB2, HER2/neu). O Grupo de alta mobilidade 1 (HMGB1) é considerado um DAMP (Padrão molecular associado ao dano) que regula a tumorigênese, proliferação e metástase maligna. A IL-33, citocina relacionada ao dano celular, tem mostrado desempenhar papel na tumorigenese e respostas inflamatórias associadas ao tumor. O objetivo do presente trabalho foi analisar a expressão de HMGB1 e IL-33 como fatores prognósticos para o CMTN. Foram avaliados dados clínicos-patológicos de 122 pacientes com diagnóstico de CMTN atendidos no Hospital Haroldo Juaçaba. Adicionalmente, foi construído um bloco de Tissue Microarray (TMA) contendo amostras de blocos de parafina de biopsias de 43 pacientes. Em seguida, foi realizada a imunofluorescência para HMGB1 com o intuito de quantificar a intensidade de expressão e o percentual de células fluorescentes com marcação citoplasmática (cHMGB1). Foi realizada a imunohistoquímica para HMGB1e IL-33 utilizando o método de detecção Kit Envision DAKO®. Na análise estatística considerou-se como significância o valor de p<0,05 utilizando o programa estatístico SPSS v.17 e GraphPad Prism v.8. A análise de dados clínico-patológicos indicou que os pacientes tinham mais de 40 anos (79%) e foram diagnosticados com carcinomas ductais de grau 2-3 (96,3%). Metástase tumoral foi observada em 1,9% dos casos. 66,7% dos pacientes com CMTN que realizaram quimioterapia adjuvante apresentaram baixa expressão de HMGB1 (p<0,05). Além disso,verificou-se que os pacientes que recidivaram, 77,8% destes tiveram baixa expressão citoplasmática de HMGB1 em comparação com os de alta expressão (p<0,05). A sobrevida global foi semelhante entre os pacientes com baixa versus alta expressão de HMGB1 citoplasmática (P=0,155). Para IL-33 não foram encontrados resultados significativos, no entanto ressaltamos que o gráfico comparativo entre expressão High e Low de IL-33 versus recidiva, mostrou que 19% dos pacientes com expressão IL-33 High apresentaram recidiva da doença (p>0,05). Assim, a expressão de HMGB1 citoplasmática apresentou associação com a recidiva e a quimioterapia adjuvante em pacientes CMTN.Valor prognóstico da expressão de HMGB1 e IL-33 em câncer de mama triplo negativoPrognostic value of HMGB1 and IL-33 expression in triple negative breast cancerinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisProteína HMGB1Neoplasias de Mama Triplo NegativasImunofluorescênciaHMGB1 ProteinTriple Negative Breast NeoplasmsFluorescent Antibody TechniqueCNPQ::CIENCIAS DA SAUDE::MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICAinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttp://lattes.cnpq.br/4698166365661939https://orcid.org/0000-0002-9741-7560http://lattes.cnpq.br/3757998764206702ORIGINAL2023_dis_fjlsales.pdf2023_dis_fjlsales.pdfapplication/pdf1438291http://repositorio.ufc.br/bitstream/riufc/74903/1/2023_dis_fjlsales.pdf28a3aa079add643049c3cb06a532d98fMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/74903/3/license.txt8a4605be74aa9ea9d79846c1fba20a33MD53riufc/749032023-11-07 13:28:00.584oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2023-11-07T16:28Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Valor prognóstico da expressão de HMGB1 e IL-33 em câncer de mama triplo negativo
dc.title.en.pt_BR.fl_str_mv Prognostic value of HMGB1 and IL-33 expression in triple negative breast cancer
title Valor prognóstico da expressão de HMGB1 e IL-33 em câncer de mama triplo negativo
spellingShingle Valor prognóstico da expressão de HMGB1 e IL-33 em câncer de mama triplo negativo
Sales, Francisca Janice Lopes
CNPQ::CIENCIAS DA SAUDE::MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
Proteína HMGB1
Neoplasias de Mama Triplo Negativas
Imunofluorescência
HMGB1 Protein
Triple Negative Breast Neoplasms
Fluorescent Antibody Technique
title_short Valor prognóstico da expressão de HMGB1 e IL-33 em câncer de mama triplo negativo
title_full Valor prognóstico da expressão de HMGB1 e IL-33 em câncer de mama triplo negativo
title_fullStr Valor prognóstico da expressão de HMGB1 e IL-33 em câncer de mama triplo negativo
title_full_unstemmed Valor prognóstico da expressão de HMGB1 e IL-33 em câncer de mama triplo negativo
title_sort Valor prognóstico da expressão de HMGB1 e IL-33 em câncer de mama triplo negativo
author Sales, Francisca Janice Lopes
author_facet Sales, Francisca Janice Lopes
author_role author
dc.contributor.author.fl_str_mv Sales, Francisca Janice Lopes
dc.contributor.advisor1.fl_str_mv Wong, Deysi Viviana Tenazoa
contributor_str_mv Wong, Deysi Viviana Tenazoa
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
topic CNPQ::CIENCIAS DA SAUDE::MEDICINA::ANATOMIA PATOLOGICA E PATOLOGIA CLINICA
Proteína HMGB1
Neoplasias de Mama Triplo Negativas
Imunofluorescência
HMGB1 Protein
Triple Negative Breast Neoplasms
Fluorescent Antibody Technique
dc.subject.ptbr.pt_BR.fl_str_mv Proteína HMGB1
Neoplasias de Mama Triplo Negativas
Imunofluorescência
dc.subject.en.pt_BR.fl_str_mv HMGB1 Protein
Triple Negative Breast Neoplasms
Fluorescent Antibody Technique
description Breast Cancer is one of the most frequent neoplasms worldwide, contributing to female morbidity and mortality. Triple Negative Breast Cancer (CMTN) is a highly aggressive subtype of cancer that is negative for estrogen and progesterone receptors and lacks overexpression of human epidermal growth factor type 2 (C-erbB2, HER2/neu). High Mobility Group 1 (HMGB1) is a DAMP (Damage Associated Molecular Pattern) that regulates tumorigenesis, proliferation, and malignant metastasis. IL-33, a cytokine related to cell damage, has been shown to play a role in tumorigenesis and tumor-associated inflammatory responses. This study aimed to analyze the expression of HMGB1 and IL-33 as prognostic factors for CMTN. Clinical-pathological data of 122 patients diagnosed with CMTN treated at Hospital Haroldo Juaçaba were evaluated. Additionally, a Tissue Microarray (TMA) block was constructed containing samples of paraffin blocks from the biopsies of 43 patients. Then, immunofluorescence for HMGB1 was performed to quantify the intensity of expression and the percentage of fluorescent cells with cytoplasmic (cHMGB1) staining. Immunohistochemistry for HMGB1 and IL-33 was performed using the Envision DAKO® Kit detection method. In the statistical analysis, significance was considered at p<0.05 using the statistical program SPSS v.17 and GraphPad Prism v.8. Analysis of clinicopathological data indicated that patients were over 40 years old (79%) and were diagnosed with grade 2-3 ductal carcinomas (96.3%). Tumor metastasis was observed in 1.9% of cases. 66.7% of patients with CMTN who underwent adjuvant chemotherapy had low expression of HMGB1 (p<0.05). Furthermore, it was found that of patients who relapsed, 77.8% of these had low cytoplasmic expression of HMGB1 compared to high expression (p<0.05). Overall survival was similar between patients with low versus high cytoplasmic HMGB1 expression (P=0.155). For IL-33, no significant results were found. However, we emphasize that the comparative graph between High and Low expression of IL-33 versus relapse showed that 19% of patients with IL-33 High expression had a disease relapse (p>0, 05). Thus, cytoplasmic HMGB1 expression was associated with relapse and adjuvant chemotherapy in CMTN patients.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-11-07T16:27:07Z
dc.date.available.fl_str_mv 2023-11-07T16:27:07Z
dc.date.issued.fl_str_mv 2023
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.citation.fl_str_mv SALES, Francisca Janice Lopes. Valor prognóstico da expressão de HMGB1 e IL-33 em câncer. 2023. Dissertação (Mestrado em Patologia) – Centro de Ciências da Saúde, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://www.repositorio.ufc.br/handle/riufc/74903. Acesso em: 07 nov. 2023.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/74903
identifier_str_mv SALES, Francisca Janice Lopes. Valor prognóstico da expressão de HMGB1 e IL-33 em câncer. 2023. Dissertação (Mestrado em Patologia) – Centro de Ciências da Saúde, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://www.repositorio.ufc.br/handle/riufc/74903. Acesso em: 07 nov. 2023.
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