Expressão da H3K9ac e H4K12ac no Adenocarcinoma Polimorfo e Carcinoma Adenoide Cístico de Glândulas Salivares

Detalhes bibliográficos
Autor(a) principal: Andrade, Aline Carla Alves Silva
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFU
Texto Completo: https://repositorio.ufu.br/handle/123456789/23189
http://dx.doi.org/10.14393/ufu.di.2018.755
Resumo: Epigenetic changes such as DNA methylation, microRNAs, and post-translational modifications (PTM) of histones have been the subject of major study for a variety of diseases, including cancer, since they are involved in the control of gene expression. Histone post-translational modifications control chromatin access to the most diverse transcription factors and thus modulate gene expression and silencing, therefore, changes in these modifications contribute to the appearance of tumors. The aim of this study was to obtain data on the presence of PTM, especially acetylation, in two of the most common malignant tumors of salivary glands that have morphohistogenetic similarities, but different behaviors: polymorphous adenocarcinoma (PAC) and adenoid cystic carcinoma (ACC). For this, we evaluated by immunohistochemistry the expression of H3K9ac and H4K12ac in 29 cases of PAC and 38 of ACC, with reference to its expression in admittedly normal non-neoplastic glandular tissue samples. For this, an index was constructed to translate absorbance intensity by nuclear area of the tumor parenchyma, called IOD. The analysis showed that IOD values for H3K9ac were significantly different between PAC (mean: 0.144; SD: ± 0.08) for the control and ACC (mean: 0.27, SD: ± 0.07) (p < 0.05). On the other hand, the values of IOD obtained for H4K12ac showed statistically significant differences for the PAC (mean: 0.114, SD: ± 0.06) and for the ACC (mean: 0.115, SD: ± 0.06) compared to controls (p < 0.05). When IOD values for H3K9ac and H4K12ac were analyzed according to predefined stratifications of clinicopathological variables, significant differences were observed for recurrent cases, which presented lower IOD values for H3K9ac than non-recurrent ones (p = 0.02). For H4K12ac, carriers of metastasis in the ACC group presented higher values than non-metastatic (p = 0.04). We found no correlation between H3K9ac and H4K12ac with cell proliferation (Ki67). It is concluded that variations in expression of these modifications may contribute to the appearance of these tumors. The results also point to the possibility that acetylation phenomena influence the behavior of the tumor. However, the results obtained require more consistency for its confirmation.
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spelling Expressão da H3K9ac e H4K12ac no Adenocarcinoma Polimorfo e Carcinoma Adenoide Cístico de Glândulas SalivaresExpression of H3K9ac and H4K12ac in the Polymorph Adenocarcinoma and Salivary Gland Cystic Adenoid CarcinomaEpigenéticaModificações de histonaAdenocarcinoma polimorfoCarcinoma adenoide císticoEpigeneticsHistone modificationsPolymorphous adenocarcinomaAdenoid cystic carcinomaCitologiaEpigenômicaHistonasCNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA::CITOLOGIA E BIOLOGIA CELULAREpigenetic changes such as DNA methylation, microRNAs, and post-translational modifications (PTM) of histones have been the subject of major study for a variety of diseases, including cancer, since they are involved in the control of gene expression. Histone post-translational modifications control chromatin access to the most diverse transcription factors and thus modulate gene expression and silencing, therefore, changes in these modifications contribute to the appearance of tumors. The aim of this study was to obtain data on the presence of PTM, especially acetylation, in two of the most common malignant tumors of salivary glands that have morphohistogenetic similarities, but different behaviors: polymorphous adenocarcinoma (PAC) and adenoid cystic carcinoma (ACC). For this, we evaluated by immunohistochemistry the expression of H3K9ac and H4K12ac in 29 cases of PAC and 38 of ACC, with reference to its expression in admittedly normal non-neoplastic glandular tissue samples. For this, an index was constructed to translate absorbance intensity by nuclear area of the tumor parenchyma, called IOD. The analysis showed that IOD values for H3K9ac were significantly different between PAC (mean: 0.144; SD: ± 0.08) for the control and ACC (mean: 0.27, SD: ± 0.07) (p < 0.05). On the other hand, the values of IOD obtained for H4K12ac showed statistically significant differences for the PAC (mean: 0.114, SD: ± 0.06) and for the ACC (mean: 0.115, SD: ± 0.06) compared to controls (p < 0.05). When IOD values for H3K9ac and H4K12ac were analyzed according to predefined stratifications of clinicopathological variables, significant differences were observed for recurrent cases, which presented lower IOD values for H3K9ac than non-recurrent ones (p = 0.02). For H4K12ac, carriers of metastasis in the ACC group presented higher values than non-metastatic (p = 0.04). We found no correlation between H3K9ac and H4K12ac with cell proliferation (Ki67). It is concluded that variations in expression of these modifications may contribute to the appearance of these tumors. The results also point to the possibility that acetylation phenomena influence the behavior of the tumor. However, the results obtained require more consistency for its confirmation.Dissertação (Mestrado)Alterações epigenéticas, como metilação do DNA, microRNAs e modificações pós-traducionais (MPT) de histonas tem sido alvo de grande estudo para as mais diversas doenças, inclusive o câncer, uma vez que estão envolvidas no controle de expressão gênica. Modificações pós-traducionais de histonas (MPTH) controlam o acesso da cromatina aos mais diversos fatores de transcrição e modulam assim a expressão e o silenciamento dos genes, e portanto, alterações em suas expressões contribuem para o aparecimento de tumores. Este trabalho teve como objetivo obter dados sobre a presença de MPTH, em especial acetilação, em dois dos mais frequentes tumores malignos de glândulas salivares que possuem similaridades morfohistogenéticas, mas comportamentos distintos: o adenocarcinoma polimorfo (ACP) e o carcinoma adenoide cístico (CAC). Para isso, avaliamos por imunohistoquímica a expressão de H3K9ac e H4K12ac em 29 casos de ACP e 38 de CAC, tendo como referência de sua expressão em amostras teciduais glandulares não neoplásicas, admitidamente normais. Para tanto, foi construído um índice traduzisse intensidade de absorbância por área nuclear do parênquima tumoral, designada IOD. As análises mostraram que valores de IOD para H3K9ac foram significativamente diferentes entre ACP (média: 0,144; DP: ± 0,08) para o controle e CAC (média: 0,27; DP: ± 0,07) (p < 0,05). Já os valores de IOD obtidos para H4K12ac apresentaram diferenças estatisticamente significativas tanto para o ACP (média: 0,114; DP: ± 0,06) como para o CAC (média: 0,115; DP: ± 0,06) comparado aos controles (p < 0,05). Quando os valores de IOD para H3K9ac e H4K12ac foram analisados segundo estratificações predefinidas das variáveis clinicopatológicas, as diferenças significativas foram observadas para os casos recidivantes, que apresentaram valores menores de IOD para H3K9ac em relação aos não recidivantes (p = 0,02). Para H4K12ac, portadores de metástase do grupo de CAC apresentaram valores maiores em relação aos não metastáticos (p = 0,04). Não encontramos correlação entre H3K9ac e H4K12ac com a proliferação celular (Ki67). Conclui-se que variações de expressão nessas modificações podem contribuir para o surgimento desses tumores. Os resultados apontam para a possiblidade de fenômenos de acetilação influenciarem no comportamento do tumor. Todavia, os resultados obtidos necessitam de maior consistência para sua confirmação.Universidade Federal de UberlândiaBrasilPrograma de Pós-graduação em Biologia Celular e Estrutural AplicadasLoyola, Adriano Motahttp://lattes.cnpq.br/5412665384225553Silva, Sindeval José dahttp://lattes.cnpq.br/7291894930505297Rosa, Roberta RezendeAndrade, Aline Carla Alves Silva2018-12-07T10:12:32Z2018-12-07T10:12:32Z2018-01-31info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfANDRADE, Aline Carla Alves Silva. Expressão da H3K9ac e H4K12ac no adenocarcinoma polimorfo e carcinoma adenoide cístico de glândulas salivares. 2018. 85 f. Dissertação (Mestrado em Biologia Celular e Estrutural Aplicadas) - Universidade Federal de Uberlândia, Uberlândia, 2018. DOI http://dx.doi.org/10.14393/ufu.di.2018.755https://repositorio.ufu.br/handle/123456789/23189http://dx.doi.org/10.14393/ufu.di.2018.755porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFUinstname:Universidade Federal de Uberlândia (UFU)instacron:UFU2018-12-07T10:13:39Zoai:repositorio.ufu.br:123456789/23189Repositório InstitucionalONGhttp://repositorio.ufu.br/oai/requestdiinf@dirbi.ufu.bropendoar:2018-12-07T10:13:39Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)false
dc.title.none.fl_str_mv Expressão da H3K9ac e H4K12ac no Adenocarcinoma Polimorfo e Carcinoma Adenoide Cístico de Glândulas Salivares
Expression of H3K9ac and H4K12ac in the Polymorph Adenocarcinoma and Salivary Gland Cystic Adenoid Carcinoma
title Expressão da H3K9ac e H4K12ac no Adenocarcinoma Polimorfo e Carcinoma Adenoide Cístico de Glândulas Salivares
spellingShingle Expressão da H3K9ac e H4K12ac no Adenocarcinoma Polimorfo e Carcinoma Adenoide Cístico de Glândulas Salivares
Andrade, Aline Carla Alves Silva
Epigenética
Modificações de histona
Adenocarcinoma polimorfo
Carcinoma adenoide cístico
Epigenetics
Histone modifications
Polymorphous adenocarcinoma
Adenoid cystic carcinoma
Citologia
Epigenômica
Histonas
CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA::CITOLOGIA E BIOLOGIA CELULAR
title_short Expressão da H3K9ac e H4K12ac no Adenocarcinoma Polimorfo e Carcinoma Adenoide Cístico de Glândulas Salivares
title_full Expressão da H3K9ac e H4K12ac no Adenocarcinoma Polimorfo e Carcinoma Adenoide Cístico de Glândulas Salivares
title_fullStr Expressão da H3K9ac e H4K12ac no Adenocarcinoma Polimorfo e Carcinoma Adenoide Cístico de Glândulas Salivares
title_full_unstemmed Expressão da H3K9ac e H4K12ac no Adenocarcinoma Polimorfo e Carcinoma Adenoide Cístico de Glândulas Salivares
title_sort Expressão da H3K9ac e H4K12ac no Adenocarcinoma Polimorfo e Carcinoma Adenoide Cístico de Glândulas Salivares
author Andrade, Aline Carla Alves Silva
author_facet Andrade, Aline Carla Alves Silva
author_role author
dc.contributor.none.fl_str_mv Loyola, Adriano Mota
http://lattes.cnpq.br/5412665384225553
Silva, Sindeval José da
http://lattes.cnpq.br/7291894930505297
Rosa, Roberta Rezende
dc.contributor.author.fl_str_mv Andrade, Aline Carla Alves Silva
dc.subject.por.fl_str_mv Epigenética
Modificações de histona
Adenocarcinoma polimorfo
Carcinoma adenoide cístico
Epigenetics
Histone modifications
Polymorphous adenocarcinoma
Adenoid cystic carcinoma
Citologia
Epigenômica
Histonas
CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA::CITOLOGIA E BIOLOGIA CELULAR
topic Epigenética
Modificações de histona
Adenocarcinoma polimorfo
Carcinoma adenoide cístico
Epigenetics
Histone modifications
Polymorphous adenocarcinoma
Adenoid cystic carcinoma
Citologia
Epigenômica
Histonas
CNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA::CITOLOGIA E BIOLOGIA CELULAR
description Epigenetic changes such as DNA methylation, microRNAs, and post-translational modifications (PTM) of histones have been the subject of major study for a variety of diseases, including cancer, since they are involved in the control of gene expression. Histone post-translational modifications control chromatin access to the most diverse transcription factors and thus modulate gene expression and silencing, therefore, changes in these modifications contribute to the appearance of tumors. The aim of this study was to obtain data on the presence of PTM, especially acetylation, in two of the most common malignant tumors of salivary glands that have morphohistogenetic similarities, but different behaviors: polymorphous adenocarcinoma (PAC) and adenoid cystic carcinoma (ACC). For this, we evaluated by immunohistochemistry the expression of H3K9ac and H4K12ac in 29 cases of PAC and 38 of ACC, with reference to its expression in admittedly normal non-neoplastic glandular tissue samples. For this, an index was constructed to translate absorbance intensity by nuclear area of the tumor parenchyma, called IOD. The analysis showed that IOD values for H3K9ac were significantly different between PAC (mean: 0.144; SD: ± 0.08) for the control and ACC (mean: 0.27, SD: ± 0.07) (p < 0.05). On the other hand, the values of IOD obtained for H4K12ac showed statistically significant differences for the PAC (mean: 0.114, SD: ± 0.06) and for the ACC (mean: 0.115, SD: ± 0.06) compared to controls (p < 0.05). When IOD values for H3K9ac and H4K12ac were analyzed according to predefined stratifications of clinicopathological variables, significant differences were observed for recurrent cases, which presented lower IOD values for H3K9ac than non-recurrent ones (p = 0.02). For H4K12ac, carriers of metastasis in the ACC group presented higher values than non-metastatic (p = 0.04). We found no correlation between H3K9ac and H4K12ac with cell proliferation (Ki67). It is concluded that variations in expression of these modifications may contribute to the appearance of these tumors. The results also point to the possibility that acetylation phenomena influence the behavior of the tumor. However, the results obtained require more consistency for its confirmation.
publishDate 2018
dc.date.none.fl_str_mv 2018-12-07T10:12:32Z
2018-12-07T10:12:32Z
2018-01-31
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
dc.identifier.uri.fl_str_mv ANDRADE, Aline Carla Alves Silva. Expressão da H3K9ac e H4K12ac no adenocarcinoma polimorfo e carcinoma adenoide cístico de glândulas salivares. 2018. 85 f. Dissertação (Mestrado em Biologia Celular e Estrutural Aplicadas) - Universidade Federal de Uberlândia, Uberlândia, 2018. DOI http://dx.doi.org/10.14393/ufu.di.2018.755
https://repositorio.ufu.br/handle/123456789/23189
http://dx.doi.org/10.14393/ufu.di.2018.755
identifier_str_mv ANDRADE, Aline Carla Alves Silva. Expressão da H3K9ac e H4K12ac no adenocarcinoma polimorfo e carcinoma adenoide cístico de glândulas salivares. 2018. 85 f. Dissertação (Mestrado em Biologia Celular e Estrutural Aplicadas) - Universidade Federal de Uberlândia, Uberlândia, 2018. DOI http://dx.doi.org/10.14393/ufu.di.2018.755
url https://repositorio.ufu.br/handle/123456789/23189
http://dx.doi.org/10.14393/ufu.di.2018.755
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Uberlândia
Brasil
Programa de Pós-graduação em Biologia Celular e Estrutural Aplicadas
publisher.none.fl_str_mv Universidade Federal de Uberlândia
Brasil
Programa de Pós-graduação em Biologia Celular e Estrutural Aplicadas
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFU
instname:Universidade Federal de Uberlândia (UFU)
instacron:UFU
instname_str Universidade Federal de Uberlândia (UFU)
instacron_str UFU
institution UFU
reponame_str Repositório Institucional da UFU
collection Repositório Institucional da UFU
repository.name.fl_str_mv Repositório Institucional da UFU - Universidade Federal de Uberlândia (UFU)
repository.mail.fl_str_mv diinf@dirbi.ufu.br
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