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Avaliação da associação de miofibroblastos e alterações dos componentes estruturais da matriz extracelular com parâmetros clinicopatológicos de queilite actínica e carcinoma de células escamosas de lábio

Detalhes bibliográficos
Ano de defesa: 2021
Autor(a) principal: Martínez, Farah Essguí Orellana
Orientador(a): Mota, Mário Rogério Lima
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
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/63107
Resumo: Actinic cheilitis (AC) is a potentially malignant disorder of the lip, whose main etiological factor is chronic exposure to ultraviolet (UV) solar radiation. UV radiation can cause genetic and extracellular matrix (ECM) changes that can contribute to the development of lip squamous cell carcinoma (LSCC). In recent years, the study of the cells that make up the tumor microenvironment (TME) has increased considerably, especially myofibroblasts (MFs), due to their role in carcinogenesis. Studies show that MFs are involved in the proliferation and invasion of malignant cells, but it is not yet clear how the changes caused by UV radiation interfere with the behavior of MFs in the process of lip carcinogenesis. Thus, the objective of this research is to evaluate the participation of MFs in lip carcinogenesis, through the correlation of clinical, histological, histomorphometric and immunohistochemical parameters, in ACs and. For this, were used 30 cases of ACs, 31 from the tumor front of LSCC and 14 healthy lips (HLs) that were arranged in blocks and prepared by tissue microarray (TMA) for immunohistochemical reactions (TGF- β, α-SMA and Ki-67) and histochemicals (Hematoxylin and Eosin, Picrosirius Red and Verhoeff Van Gienson). Collection of clinical data and histopathological grading of epithelial dysplasias in ACs were performed using the binary system and the system established by Bryne for LSCC. The areas of solar elastosis in the ACs were analyzed histomorphometrically (degree, extension, depth, and distance to the dysplastic epithelium). The fronts of the LSCCs were analyzed in search of perineural and angiolymphatic invasion. The data were expressed as means and standard deviations, sub mitted to the Kolmogorov-Smirnov test, compared by the Mann-Whitney, Kruskal-Wallis / Dunn tests, and finally correlated in their clinical, histological, immunohistochemical and histomorphometric data by the Spearman test. (SPSS, p <0.05). The analyzes of the ACs showed a greater number of α-SMA + cells in relation to samples of HLs (p = 0.034), and these cells (located in the areas without elastosis) were associated with the vertical expansion of the elastosis itself (p = 0.027). Additionally, it was found that the areas of solar elastosis showed less collagen deposition (p <0.001) and immunostaining for TGF-β (p <0.001), and higher density of elastic fibers (p <0.05), compared with areas without elastosis. Still in ACs, there was a positive correlation between high-risk dysplasias and the proximity of solar elastosis to the dysplastic epithelium (p = 0.027). The analysis of the LSCCs showed a higher number of α-SMA + cells in relation to samples of HLs (p = 0.034), in addition to the reduction in the deposition of total collagen (p = 0.009) and type I collagen (p <0.001) in relation to the ACs and HLs. There was also a negative correlation between the amount of α-SMA + cells and the deposition of total collagen (p = 0.041) and type III collagen (p = 0.041). We also observed that the collagen loss and elastic density was significantly greater in tumors of larger size (p = 0.045) and with nodal metastasis (p = 0.047). Our findings provide evidence of the possible role of myofibroblasts, collagen fibers and areas of elastosis in the process of lip carcinogenesis.
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spelling Martínez, Farah Essguí OrellanaBezerra, Thâmara Manoela MarinhoMota, Mário Rogério Lima2021-12-17T17:23:09Z2021-12-17T17:23:09Z2021-05-17MARTÍNEZ. F. E. O. Avaliação da associação de miofibroblastos e alterações dos componentes estruturais da matriz extracelular com parâmetros clinicopatológicos de queilite actínica e carcinoma de células escamosas de lábio. 2021. 78 f. Dissertação (Mestrado em Odontologia) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2021. Disponível em: http://www.repositorio.ufc.br/handle/riufc/63107. Acesso em: 17/12/2021.http://www.repositorio.ufc.br/handle/riufc/63107Actinic cheilitis (AC) is a potentially malignant disorder of the lip, whose main etiological factor is chronic exposure to ultraviolet (UV) solar radiation. UV radiation can cause genetic and extracellular matrix (ECM) changes that can contribute to the development of lip squamous cell carcinoma (LSCC). In recent years, the study of the cells that make up the tumor microenvironment (TME) has increased considerably, especially myofibroblasts (MFs), due to their role in carcinogenesis. Studies show that MFs are involved in the proliferation and invasion of malignant cells, but it is not yet clear how the changes caused by UV radiation interfere with the behavior of MFs in the process of lip carcinogenesis. Thus, the objective of this research is to evaluate the participation of MFs in lip carcinogenesis, through the correlation of clinical, histological, histomorphometric and immunohistochemical parameters, in ACs and. For this, were used 30 cases of ACs, 31 from the tumor front of LSCC and 14 healthy lips (HLs) that were arranged in blocks and prepared by tissue microarray (TMA) for immunohistochemical reactions (TGF- β, α-SMA and Ki-67) and histochemicals (Hematoxylin and Eosin, Picrosirius Red and Verhoeff Van Gienson). Collection of clinical data and histopathological grading of epithelial dysplasias in ACs were performed using the binary system and the system established by Bryne for LSCC. The areas of solar elastosis in the ACs were analyzed histomorphometrically (degree, extension, depth, and distance to the dysplastic epithelium). The fronts of the LSCCs were analyzed in search of perineural and angiolymphatic invasion. The data were expressed as means and standard deviations, sub mitted to the Kolmogorov-Smirnov test, compared by the Mann-Whitney, Kruskal-Wallis / Dunn tests, and finally correlated in their clinical, histological, immunohistochemical and histomorphometric data by the Spearman test. (SPSS, p <0.05). The analyzes of the ACs showed a greater number of α-SMA + cells in relation to samples of HLs (p = 0.034), and these cells (located in the areas without elastosis) were associated with the vertical expansion of the elastosis itself (p = 0.027). Additionally, it was found that the areas of solar elastosis showed less collagen deposition (p <0.001) and immunostaining for TGF-β (p <0.001), and higher density of elastic fibers (p <0.05), compared with areas without elastosis. Still in ACs, there was a positive correlation between high-risk dysplasias and the proximity of solar elastosis to the dysplastic epithelium (p = 0.027). The analysis of the LSCCs showed a higher number of α-SMA + cells in relation to samples of HLs (p = 0.034), in addition to the reduction in the deposition of total collagen (p = 0.009) and type I collagen (p <0.001) in relation to the ACs and HLs. There was also a negative correlation between the amount of α-SMA + cells and the deposition of total collagen (p = 0.041) and type III collagen (p = 0.041). We also observed that the collagen loss and elastic density was significantly greater in tumors of larger size (p = 0.045) and with nodal metastasis (p = 0.047). Our findings provide evidence of the possible role of myofibroblasts, collagen fibers and areas of elastosis in the process of lip carcinogenesis.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES - Demanda SocialA queilite actínica (QA) é uma desordem potencialmente maligna do lábio, que tem como principal fator etiológico a exposição crônica à radiação solar ultravioleta (UV). A radiação UV é capaz de ocasionar alterações genéticas e da matriz extracelular (MEC) que podem contribuir ao desenvolvimento do carcinoma de células escamosas do lábio (CCEL). Nos últimos anos, o estudo das células que compõem o microambiente tumoral (MT) aumentou consideravelmente, em especial os miofibroblastos (MFs). Estudos mostram que MFs estão envolvidos na proliferação e invasão de células malignas, porém ainda não é claro como as alterações causadas pela radiação UV interferem no seu comportamento e no processo de carcinogênese labial. Dessa forma, constitui o objetivo desta pesquisa avaliar a participação dos MFs na carcinogênese labial, através da correlação de parâmetros clínicos, histológicos, histomorfométricos e imunoistoquímicos, em QAs e CCELs. Para isso, foram selecionados 30 casos de QAs, 30 CCELs do front tumoral e 15 lábios sadios (LSs) os quais foram preparados por Tissue Micro Array (TMA), dispostos em um único bloco para reações imunoistoquímicas (TGF-β, α-AML e Ki-67) e histoquímicas (Hematoxilina e Eosina, Picrosirius Red e Verhoeff Van Gienson). Coleta de dados clínicos e gradação histopatológica das displasias epiteliais em QAs foram realizadas a através do sistema binário e pelo sistema estabelecido por Bryne para CCELs. As áreas de elastose solar das QAs foram analisadas histomorfometricamente (grau, extensão, profundidade e distância para o epitélio displásico). Os fronts dos CCELs foram analisados na busca de invasão perineural e angiolinfática. Os dados foram expressos em forma de média e desvio-padrão, submetidos ao teste Kolmogorov-Smirnov, comparados pelos testes de Mann-Whitney, Kruskal-Wallis/Dunn e Spearman (SPSS, p<0,05). As análises das QAs apresentaram maior número de células α-AML+ em relação a amostras de LSs (p= 0,034), e estas células (localizados nas áreas sem elastose) foram associadas com a expansão vertical da própria elastose (p=0,027). Adicionalmente, verificou-se que as áreas de elastose solar apresentaram menor deposição de colágeno (p<0.001) e imunomarcação para TGF-β (p<0.001) e maior densidade de fibras elásticas (p<0.05), quando comparadas com as áreas sem elastose. Em QAs, observou-se uma correlação positiva entre displasias de alto risco a proximidade da elastose solar ao epitélio displásico (p= 0,027). As análises dos CCELs apresentaram maior número de células α-AML+ em relação a amostras de LSs (p= 0,034), além da redução da deposição de colágeno total (p= 0,009) e colágeno tipo I (p<0.001) em relação as QAs e LSs. Verificou-se, ainda, uma correlação negativa entre a quantidade de células α-AML+ e a deposição de colágeno total (p= 0.041) e colágeno tipo III (p= 0.041). Observou-se, ainda, que a perda colagênica e de densidade elástica foi significantemente maior em tumores de maior tamanho (p= 0.045) e com metástase nodal (p= 0.047). Este estudo evidenciou o possível papel dos MFs, das fibras colágenas e das áreas de elastose no processo de carcinogênese de lábio.Neoplasias BucaisLábioFibroblastosCarcinoma de Células EscamosasMicroambiente TumoralAvaliação da associação de miofibroblastos e alterações dos componentes estruturais da matriz extracelular com parâmetros clinicopatológicos de queilite actínica e carcinoma de células escamosas de lábioinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessORIGINAL2021_dis_feomartinez.pdf2021_dis_feomartinez.pdfapplication/pdf2383813http://repositorio.ufc.br/bitstream/riufc/63107/5/2021_dis_feomartinez.pdfd0101ec7587466c4db21ef435ff622ddMD55LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/63107/4/license.txt8a4605be74aa9ea9d79846c1fba20a33MD54riufc/631072023-09-18 07:58:04.924oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2023-09-18T10:58:04Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Avaliação da associação de miofibroblastos e alterações dos componentes estruturais da matriz extracelular com parâmetros clinicopatológicos de queilite actínica e carcinoma de células escamosas de lábio
title Avaliação da associação de miofibroblastos e alterações dos componentes estruturais da matriz extracelular com parâmetros clinicopatológicos de queilite actínica e carcinoma de células escamosas de lábio
spellingShingle Avaliação da associação de miofibroblastos e alterações dos componentes estruturais da matriz extracelular com parâmetros clinicopatológicos de queilite actínica e carcinoma de células escamosas de lábio
Martínez, Farah Essguí Orellana
Neoplasias Bucais
Lábio
Fibroblastos
Carcinoma de Células Escamosas
Microambiente Tumoral
title_short Avaliação da associação de miofibroblastos e alterações dos componentes estruturais da matriz extracelular com parâmetros clinicopatológicos de queilite actínica e carcinoma de células escamosas de lábio
title_full Avaliação da associação de miofibroblastos e alterações dos componentes estruturais da matriz extracelular com parâmetros clinicopatológicos de queilite actínica e carcinoma de células escamosas de lábio
title_fullStr Avaliação da associação de miofibroblastos e alterações dos componentes estruturais da matriz extracelular com parâmetros clinicopatológicos de queilite actínica e carcinoma de células escamosas de lábio
title_full_unstemmed Avaliação da associação de miofibroblastos e alterações dos componentes estruturais da matriz extracelular com parâmetros clinicopatológicos de queilite actínica e carcinoma de células escamosas de lábio
title_sort Avaliação da associação de miofibroblastos e alterações dos componentes estruturais da matriz extracelular com parâmetros clinicopatológicos de queilite actínica e carcinoma de células escamosas de lábio
author Martínez, Farah Essguí Orellana
author_facet Martínez, Farah Essguí Orellana
author_role author
dc.contributor.co-advisor.none.fl_str_mv Bezerra, Thâmara Manoela Marinho
dc.contributor.author.fl_str_mv Martínez, Farah Essguí Orellana
dc.contributor.advisor1.fl_str_mv Mota, Mário Rogério Lima
contributor_str_mv Mota, Mário Rogério Lima
dc.subject.por.fl_str_mv Neoplasias Bucais
Lábio
Fibroblastos
Carcinoma de Células Escamosas
Microambiente Tumoral
topic Neoplasias Bucais
Lábio
Fibroblastos
Carcinoma de Células Escamosas
Microambiente Tumoral
description Actinic cheilitis (AC) is a potentially malignant disorder of the lip, whose main etiological factor is chronic exposure to ultraviolet (UV) solar radiation. UV radiation can cause genetic and extracellular matrix (ECM) changes that can contribute to the development of lip squamous cell carcinoma (LSCC). In recent years, the study of the cells that make up the tumor microenvironment (TME) has increased considerably, especially myofibroblasts (MFs), due to their role in carcinogenesis. Studies show that MFs are involved in the proliferation and invasion of malignant cells, but it is not yet clear how the changes caused by UV radiation interfere with the behavior of MFs in the process of lip carcinogenesis. Thus, the objective of this research is to evaluate the participation of MFs in lip carcinogenesis, through the correlation of clinical, histological, histomorphometric and immunohistochemical parameters, in ACs and. For this, were used 30 cases of ACs, 31 from the tumor front of LSCC and 14 healthy lips (HLs) that were arranged in blocks and prepared by tissue microarray (TMA) for immunohistochemical reactions (TGF- β, α-SMA and Ki-67) and histochemicals (Hematoxylin and Eosin, Picrosirius Red and Verhoeff Van Gienson). Collection of clinical data and histopathological grading of epithelial dysplasias in ACs were performed using the binary system and the system established by Bryne for LSCC. The areas of solar elastosis in the ACs were analyzed histomorphometrically (degree, extension, depth, and distance to the dysplastic epithelium). The fronts of the LSCCs were analyzed in search of perineural and angiolymphatic invasion. The data were expressed as means and standard deviations, sub mitted to the Kolmogorov-Smirnov test, compared by the Mann-Whitney, Kruskal-Wallis / Dunn tests, and finally correlated in their clinical, histological, immunohistochemical and histomorphometric data by the Spearman test. (SPSS, p <0.05). The analyzes of the ACs showed a greater number of α-SMA + cells in relation to samples of HLs (p = 0.034), and these cells (located in the areas without elastosis) were associated with the vertical expansion of the elastosis itself (p = 0.027). Additionally, it was found that the areas of solar elastosis showed less collagen deposition (p <0.001) and immunostaining for TGF-β (p <0.001), and higher density of elastic fibers (p <0.05), compared with areas without elastosis. Still in ACs, there was a positive correlation between high-risk dysplasias and the proximity of solar elastosis to the dysplastic epithelium (p = 0.027). The analysis of the LSCCs showed a higher number of α-SMA + cells in relation to samples of HLs (p = 0.034), in addition to the reduction in the deposition of total collagen (p = 0.009) and type I collagen (p <0.001) in relation to the ACs and HLs. There was also a negative correlation between the amount of α-SMA + cells and the deposition of total collagen (p = 0.041) and type III collagen (p = 0.041). We also observed that the collagen loss and elastic density was significantly greater in tumors of larger size (p = 0.045) and with nodal metastasis (p = 0.047). Our findings provide evidence of the possible role of myofibroblasts, collagen fibers and areas of elastosis in the process of lip carcinogenesis.
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-12-17T17:23:09Z
dc.date.available.fl_str_mv 2021-12-17T17:23:09Z
dc.date.issued.fl_str_mv 2021-05-17
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.citation.fl_str_mv MARTÍNEZ. F. E. O. Avaliação da associação de miofibroblastos e alterações dos componentes estruturais da matriz extracelular com parâmetros clinicopatológicos de queilite actínica e carcinoma de células escamosas de lábio. 2021. 78 f. Dissertação (Mestrado em Odontologia) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2021. Disponível em: http://www.repositorio.ufc.br/handle/riufc/63107. Acesso em: 17/12/2021.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/63107
identifier_str_mv MARTÍNEZ. F. E. O. Avaliação da associação de miofibroblastos e alterações dos componentes estruturais da matriz extracelular com parâmetros clinicopatológicos de queilite actínica e carcinoma de células escamosas de lábio. 2021. 78 f. Dissertação (Mestrado em Odontologia) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2021. Disponível em: http://www.repositorio.ufc.br/handle/riufc/63107. Acesso em: 17/12/2021.
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