Análise da imunoexpressão das proteínas de reparo do DNA mismatch repair (MMR) na carcinogênese do vermelhão do lábio

Detalhes bibliográficos
Ano de defesa: 2021
Autor(a) principal: Barragán, Yamyle Claudia Velasquez
Orientador(a): Silva, Paulo Goberlânio de Barros
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/59799
Resumo: Squamous cell carcinoma (SCC) of the lip usually appears after actinic cheilitis (AC), the main precursor lesion. Overexposure to type A and B ultraviolet sun rays causes DNA mutations that lead to alterations in DNA repair proteins, especially those of the Mismatch Repair (MMR) complex. This family of proteins is related to post-replicational DNA repair, correcting nitrogenous bases incorrectly incorporated into the genome through its two main heterodimers (MutSα: MSH2 and MSH6; MutLα: PMS2 and MLH1). In this context, this project aimed to analyze the immunoexpression of these MMR complex proteins in the carcinogenesis of lip vermilion. An analytical cross-sectional study was carried out with biopsies from the Ceará Cancer Institute (ICC), in which healthy lip epithelia from pelveglossectomies (15 cases), QA (30 cases) and CEC of the lip (45 cases) were selected. were subjected to immunohistochemistry for MSH2, MSH6, PMS2, MLH1 and ki-67. Clinical-prognostic variables such as sex, age, place of birth, origin, entry into the service (public or private), occupation, history of smoking or alcohol consumption, TNM staging, recurrence and therapeutic protocol were also evaluated. The groups were compared using the Mann-Whitney or Kruskal-Wallis/Dunn tests between study groups and between clinical and prognostic data. SCC and QA showed a significant increase in immunoexpression for MutSα (p<0.001), MSH6 (p<0.001) and MLH1 (p=0.040) and in the MSH2/MSH6 ratio (p<0.001). The MSH2/MSH6 ratio in QA was greater than the PMS2/MLH1 ratio (p=0.028). AK with high-risk dysplasia (p=0.024) and SCC with vascular invasion (p=0.035) had lower immunoexpression for MSH6. T3/T4 tumors had higher MutSα (p=0.028) and MutLα (p=0.014) ratios and, in patients with nodal metastasis, the MutLα ratio was significantly higher than the MSH2/MSH6 ratio (p=0.046). This study demonstrated that the process of lip carcinogenesis (CEC) is related to alterations in the immunoexpression of MUTSα and MUTLα proteins.
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spelling Barragán, Yamyle Claudia VelasquezSilva, Paulo Goberlânio de Barros2021-08-02T11:26:18Z2021-08-02T11:26:18Z2021-06-11BARRAGÁN, Y. C. V. Análise da imunoexpressão das proteínas de reparo do DNA mismatch repair (MMR) na carcinogênese do vermelhão do lábio. 2021. 61 f. Dissertação (Mestrado em Odontologia) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2021http://www.repositorio.ufc.br/handle/riufc/59799Squamous cell carcinoma (SCC) of the lip usually appears after actinic cheilitis (AC), the main precursor lesion. Overexposure to type A and B ultraviolet sun rays causes DNA mutations that lead to alterations in DNA repair proteins, especially those of the Mismatch Repair (MMR) complex. This family of proteins is related to post-replicational DNA repair, correcting nitrogenous bases incorrectly incorporated into the genome through its two main heterodimers (MutSα: MSH2 and MSH6; MutLα: PMS2 and MLH1). In this context, this project aimed to analyze the immunoexpression of these MMR complex proteins in the carcinogenesis of lip vermilion. An analytical cross-sectional study was carried out with biopsies from the Ceará Cancer Institute (ICC), in which healthy lip epithelia from pelveglossectomies (15 cases), QA (30 cases) and CEC of the lip (45 cases) were selected. were subjected to immunohistochemistry for MSH2, MSH6, PMS2, MLH1 and ki-67. Clinical-prognostic variables such as sex, age, place of birth, origin, entry into the service (public or private), occupation, history of smoking or alcohol consumption, TNM staging, recurrence and therapeutic protocol were also evaluated. The groups were compared using the Mann-Whitney or Kruskal-Wallis/Dunn tests between study groups and between clinical and prognostic data. SCC and QA showed a significant increase in immunoexpression for MutSα (p<0.001), MSH6 (p<0.001) and MLH1 (p=0.040) and in the MSH2/MSH6 ratio (p<0.001). The MSH2/MSH6 ratio in QA was greater than the PMS2/MLH1 ratio (p=0.028). AK with high-risk dysplasia (p=0.024) and SCC with vascular invasion (p=0.035) had lower immunoexpression for MSH6. T3/T4 tumors had higher MutSα (p=0.028) and MutLα (p=0.014) ratios and, in patients with nodal metastasis, the MutLα ratio was significantly higher than the MSH2/MSH6 ratio (p=0.046). This study demonstrated that the process of lip carcinogenesis (CEC) is related to alterations in the immunoexpression of MUTSα and MUTLα proteins.O carcinoma espinocelular (CEC) do lábio geralmente surge após a queilite actínica (QA), a principal lesão precursora. A superexposição aos raios solares ultravioleta tipos A e B causa mutações no DNA que levam a alterações em proteínas de reparo do DNA, principalmente aquelas do complexo Mismatch Repair (MMR). Essa família de proteínas está relacionada ao reparo pós replicacional do DNA, corrigindo as bases nitrogenadas incorporadas incorretamente ao genoma por meio dos seus dois principais heterodímeros (MutSα: MSH2 e MSH6; MutLα: PMS2 e MLH1). Nesse contexto, este projeto teve como objetivo analisar a imunoexpressão dessas proteínas do complexo MMR na carcinogênese do vermelhão do lábio. Foi realizado um estudo transversal analítico com biopsias do Instituto do Câncer do Ceará (ICC), em que foram selecionados epitélios sadios de lábio oriundos de pelveglossectomias (15 casos), QA (30 casos) e CEC de lábio (45 casos), as quais foram submetidas à imuno-histoquímica para MSH2, MSH6, PMS2, MLH1 e ki-67. Variáveis clínico-prognósticas como sexo, idade, naturalidade, procedência, entrada no serviço (pública ou privada), profissão, histórico de fumo ou etilismo, estadiamento TNM, recidiva e protocolo terapêutico também foram avaliadas. Os grupos foram comparados por meio dos testes Mann-Whitney ou Kruskal-Wallis/Dunn entre grupos de estudo e entre os dados clínico-prognósticos. O CEC e a QA apresentaram aumento significativo na imunoexpressão para MutSα (p<0,001), MSH6 (p<0,001) e MLH1 (p=0,040) e na razão MSH2/MSH6 (p<0,001). A razão MSH2/MSH6, na QA, foi maior que a razão PMS2/MLH1 (p=0,028). As QA com displasia de alto risco (p=0,024) e os CEC com invasão vascular (p=0,035) apresentaram menor imunoexpressão para MSH6. Tumores T3/T4 apresentaram maior razão MutSα (p=0,028) e MutLα (p=0,014) e, nos pacientes com metástase nodal, a razão MutLα foi significantemente maior que a razão MSH2/MSH6 (p=0,046). Este estudo demonstrou que o processo de carcinogênese do lábio (CEC) está relacionado a alterações na imunoexpressão das proteínas MUTSα e MUTLα.LábioNeoplasias bucaisProteínas MutSProteínas MutLAnálise da imunoexpressão das proteínas de reparo do DNA mismatch repair (MMR) na carcinogênese do vermelhão do 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_barragán.pdf2021_dis_barragán.pdfapplication/pdf744441http://repositorio.ufc.br/bitstream/riufc/59799/1/2021_dis_barrag%c3%a1n.pdf181e61137c71ead74f22e3cd2fbaff9aMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/59799/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52riufc/597992021-08-02 08:26:18.229oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2021-08-02T11:26:18Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Análise da imunoexpressão das proteínas de reparo do DNA mismatch repair (MMR) na carcinogênese do vermelhão do lábio
title Análise da imunoexpressão das proteínas de reparo do DNA mismatch repair (MMR) na carcinogênese do vermelhão do lábio
spellingShingle Análise da imunoexpressão das proteínas de reparo do DNA mismatch repair (MMR) na carcinogênese do vermelhão do lábio
Barragán, Yamyle Claudia Velasquez
Lábio
Neoplasias bucais
Proteínas MutS
Proteínas MutL
title_short Análise da imunoexpressão das proteínas de reparo do DNA mismatch repair (MMR) na carcinogênese do vermelhão do lábio
title_full Análise da imunoexpressão das proteínas de reparo do DNA mismatch repair (MMR) na carcinogênese do vermelhão do lábio
title_fullStr Análise da imunoexpressão das proteínas de reparo do DNA mismatch repair (MMR) na carcinogênese do vermelhão do lábio
title_full_unstemmed Análise da imunoexpressão das proteínas de reparo do DNA mismatch repair (MMR) na carcinogênese do vermelhão do lábio
title_sort Análise da imunoexpressão das proteínas de reparo do DNA mismatch repair (MMR) na carcinogênese do vermelhão do lábio
author Barragán, Yamyle Claudia Velasquez
author_facet Barragán, Yamyle Claudia Velasquez
author_role author
dc.contributor.author.fl_str_mv Barragán, Yamyle Claudia Velasquez
dc.contributor.advisor1.fl_str_mv Silva, Paulo Goberlânio de Barros
contributor_str_mv Silva, Paulo Goberlânio de Barros
dc.subject.por.fl_str_mv Lábio
Neoplasias bucais
Proteínas MutS
Proteínas MutL
topic Lábio
Neoplasias bucais
Proteínas MutS
Proteínas MutL
description Squamous cell carcinoma (SCC) of the lip usually appears after actinic cheilitis (AC), the main precursor lesion. Overexposure to type A and B ultraviolet sun rays causes DNA mutations that lead to alterations in DNA repair proteins, especially those of the Mismatch Repair (MMR) complex. This family of proteins is related to post-replicational DNA repair, correcting nitrogenous bases incorrectly incorporated into the genome through its two main heterodimers (MutSα: MSH2 and MSH6; MutLα: PMS2 and MLH1). In this context, this project aimed to analyze the immunoexpression of these MMR complex proteins in the carcinogenesis of lip vermilion. An analytical cross-sectional study was carried out with biopsies from the Ceará Cancer Institute (ICC), in which healthy lip epithelia from pelveglossectomies (15 cases), QA (30 cases) and CEC of the lip (45 cases) were selected. were subjected to immunohistochemistry for MSH2, MSH6, PMS2, MLH1 and ki-67. Clinical-prognostic variables such as sex, age, place of birth, origin, entry into the service (public or private), occupation, history of smoking or alcohol consumption, TNM staging, recurrence and therapeutic protocol were also evaluated. The groups were compared using the Mann-Whitney or Kruskal-Wallis/Dunn tests between study groups and between clinical and prognostic data. SCC and QA showed a significant increase in immunoexpression for MutSα (p<0.001), MSH6 (p<0.001) and MLH1 (p=0.040) and in the MSH2/MSH6 ratio (p<0.001). The MSH2/MSH6 ratio in QA was greater than the PMS2/MLH1 ratio (p=0.028). AK with high-risk dysplasia (p=0.024) and SCC with vascular invasion (p=0.035) had lower immunoexpression for MSH6. T3/T4 tumors had higher MutSα (p=0.028) and MutLα (p=0.014) ratios and, in patients with nodal metastasis, the MutLα ratio was significantly higher than the MSH2/MSH6 ratio (p=0.046). This study demonstrated that the process of lip carcinogenesis (CEC) is related to alterations in the immunoexpression of MUTSα and MUTLα proteins.
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-08-02T11:26:18Z
dc.date.available.fl_str_mv 2021-08-02T11:26:18Z
dc.date.issued.fl_str_mv 2021-06-11
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.identifier.citation.fl_str_mv BARRAGÁN, Y. C. V. Análise da imunoexpressão das proteínas de reparo do DNA mismatch repair (MMR) na carcinogênese do vermelhão do lábio. 2021. 61 f. Dissertação (Mestrado em Odontologia) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2021
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/59799
identifier_str_mv BARRAGÁN, Y. C. V. Análise da imunoexpressão das proteínas de reparo do DNA mismatch repair (MMR) na carcinogênese do vermelhão do lábio. 2021. 61 f. Dissertação (Mestrado em Odontologia) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2021
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