Análise da imunoexpressão de proteínas relacionadas à autofagia (Atg7, LC3A, p62 e p-mTOR) em neoplasias de glândulas salivares
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UEPB |
Texto Completo: | http://tede.bc.uepb.edu.br/jspui/handle/tede/3861 |
Resumo: | Pleomorphic adenoma (PA), polymorphous adenocarcinoma (PAC), mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are salivary gland neoplasms that exhibit important differences in their etiopathogenesis, histopathological characteristics and clinical behaviors. In the context of neoplastic development and progression, studies have highlighted the participation of an intracellular catabolic mechanism involved in physiological and pathological processes, denominated autophagy. This mechanism involves several molecules, with emphasis on Atg7, LC3, p62 and p-mTOR proteins. Investigations on autophagy in salivary gland neoplasms are recent and directed, especially, at ACC. In addition, these studies analyzed a small number of autophagy-related proteins, with emphasis on LC3 and mTOR. Thus, the objective of this study was to evaluate the immunoexpression of four autophagy-related proteins (Atg7, LC3A, p62 and p-mTOR) in PAs, PACs, MECs and ACCs of salivary glands. The sample consisted of 20 PAs, 20 PACs, 20 MECs and 14 ACCs. In the morphological study, the histopathological subtypes of PAs (cell-rich and cell-poor) (SOARES et al., 2009) and ACCs (cribriform, tubular and solid) (ELLIS; AUCLAIR, 2008) were analyzed. According to the histopathological grade of malignancy, MECs were classified as: grade I, grade II and grade III (BRANDWEIN et al., 2001). In the immunohistochemical study, the percentages of positive neoplastic cells (cytoplasm and nucleus) in 5 fields of highest immunoreactivity (400) for anti-Atg7, anti-LC3A, anti-p62 and anti-p-mTOR antibodies were determined (OUYANG et al., 2017). The data obtained were statistically analyzed using the Mann-Whitney test and Spearman’s correlation test (p < 0.05). There was a higher frequency of cell-rich PAs (60.0%) and cribriform (42.85%) and tubular (42.85%) ACCs. Regarding the histopathological grade of malignancy of MECs, there was a predominance of cases with grade I (45.0%) and grade II (45.0%). Cytoplasmic expression of Atg7 was observed in all groups analyzed, with high median percentages of positivity. For LC3A, cytoplasmic immunopositivity was found in most PACs (95.0%) and in all cases of PA, MEC and ACC. Regarding p62, the lowest percentages of cytoplasmic expression were observed in PAs and ACCs, both with significant difference compared to PACs and MECs (p < 0.05). The highest percentages of nuclear expression of p62 were observed in PAs, with statistically significant difference compared to PACs and ACCs (p < 0.005). ACCs showed lower percentages of cytoplasmic positivity for p-mTOR compared to other groups of lesions (p < 0.005). Regarding nuclear expression of Atg7, LC3A and p-mTOR, all groups exhibited low median percentages of positivity. There were no statistically significant differences in the immunoexpression of autophagy-related proteins according to the histopathological subtypes of PAs and ACCs and the histopathological grade of malignancy of MECs. In PAs, MECs and ACCs, positive correlations were observed between the immunoexpressions of autophagy-related proteins (p < 0.05). In conclusion, the results of this study suggest the potential involvement of autophagy in the pathogenesis of PA, PAC, CME and ACC of salivary glands. The upregulation of autophagy and the reduced nuclear translocation of protein p62 may contribute to aggressive biological behavior of ACC of salivary glands. |
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Nonaka, Cassiano Francisco Weegehttp://lattes.cnpq.br/0224522010734716Bonan, Paulo Rogério Ferretihttp://lattes.cnpq.br/4201967424037508Godoy, Gustavo Pinahttp://lattes.cnpq.br/5655149996985928Costa, Edja Maria Melo de Britohttp://lattes.cnpq.br/0192415370217147Gordón-Núñez, Manuel Antoniohttp://lattes.cnpq.br/6553619409299152Nonaka, Cassiano Francisco Weegehttp://lattes.cnpq.br/0224522010734716http://lattes.cnpq.br/4390246107391803Pires, Emanuene Galdino2021-11-24T23:35:14Z2021-12-092020-12-09Pires, Emanuene Galdino. Análise da imunoexpressão de proteínas relacionadas à autofagia (Atg7, LC3A, p62 e p-mTOR) em neoplasias de glândulas salivares. 2020. 100p. Tese (Programa de Pós-Graduação em Odontologia - PPGO) - Universidade Estadual da Paraíba, Campina Grande.http://tede.bc.uepb.edu.br/jspui/handle/tede/3861Pleomorphic adenoma (PA), polymorphous adenocarcinoma (PAC), mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are salivary gland neoplasms that exhibit important differences in their etiopathogenesis, histopathological characteristics and clinical behaviors. In the context of neoplastic development and progression, studies have highlighted the participation of an intracellular catabolic mechanism involved in physiological and pathological processes, denominated autophagy. This mechanism involves several molecules, with emphasis on Atg7, LC3, p62 and p-mTOR proteins. Investigations on autophagy in salivary gland neoplasms are recent and directed, especially, at ACC. In addition, these studies analyzed a small number of autophagy-related proteins, with emphasis on LC3 and mTOR. Thus, the objective of this study was to evaluate the immunoexpression of four autophagy-related proteins (Atg7, LC3A, p62 and p-mTOR) in PAs, PACs, MECs and ACCs of salivary glands. The sample consisted of 20 PAs, 20 PACs, 20 MECs and 14 ACCs. In the morphological study, the histopathological subtypes of PAs (cell-rich and cell-poor) (SOARES et al., 2009) and ACCs (cribriform, tubular and solid) (ELLIS; AUCLAIR, 2008) were analyzed. According to the histopathological grade of malignancy, MECs were classified as: grade I, grade II and grade III (BRANDWEIN et al., 2001). In the immunohistochemical study, the percentages of positive neoplastic cells (cytoplasm and nucleus) in 5 fields of highest immunoreactivity (400) for anti-Atg7, anti-LC3A, anti-p62 and anti-p-mTOR antibodies were determined (OUYANG et al., 2017). The data obtained were statistically analyzed using the Mann-Whitney test and Spearman’s correlation test (p < 0.05). There was a higher frequency of cell-rich PAs (60.0%) and cribriform (42.85%) and tubular (42.85%) ACCs. Regarding the histopathological grade of malignancy of MECs, there was a predominance of cases with grade I (45.0%) and grade II (45.0%). Cytoplasmic expression of Atg7 was observed in all groups analyzed, with high median percentages of positivity. For LC3A, cytoplasmic immunopositivity was found in most PACs (95.0%) and in all cases of PA, MEC and ACC. Regarding p62, the lowest percentages of cytoplasmic expression were observed in PAs and ACCs, both with significant difference compared to PACs and MECs (p < 0.05). The highest percentages of nuclear expression of p62 were observed in PAs, with statistically significant difference compared to PACs and ACCs (p < 0.005). ACCs showed lower percentages of cytoplasmic positivity for p-mTOR compared to other groups of lesions (p < 0.005). Regarding nuclear expression of Atg7, LC3A and p-mTOR, all groups exhibited low median percentages of positivity. There were no statistically significant differences in the immunoexpression of autophagy-related proteins according to the histopathological subtypes of PAs and ACCs and the histopathological grade of malignancy of MECs. In PAs, MECs and ACCs, positive correlations were observed between the immunoexpressions of autophagy-related proteins (p < 0.05). In conclusion, the results of this study suggest the potential involvement of autophagy in the pathogenesis of PA, PAC, CME and ACC of salivary glands. The upregulation of autophagy and the reduced nuclear translocation of protein p62 may contribute to aggressive biological behavior of ACC of salivary glands.O adenoma pleomórfico (AP), o adenocarcinoma polimorfo (ACP), o carcinoma mucoepidermoide (CME) e o carcinoma adenoide cístico (CAC) são neoplasias de glândulas salivares que apresentam importantes diferenças na sua etiopatogênese, características histopatológicas e comportamentos clínicos. No contexto do desenvolvimento e progressão de neoplasias, estudos têm destacado a participação de um mecanismo intracelular catabólico que atua em processos fisiológicos e patológicos, denominado autofagia. Esse mecanismo envolve a participação de diversas moléculas, com destaque para as proteínas Atg7, LC3, p62 e p-mTOR. Pesquisas sobre a autofagia em neoplasias de glândulas salivares são recentes e direcionadas, especialmente, ao CAC. Além disso, esses estudos analisaram um pequeno número de proteínas relacionadas à autofagia, com destaque para LC3 e mTOR. Assim, o presente estudo objetivou avaliar a imunoexpressão de quatro proteínas relacionadas à autofagia (Atg7, LC3A, p62 e p-mTOR) em APs, ACPs, CMEs e CACs de glândulas salivares. A amostra foi constituída por 20 APs, 20 ACPs, 20 CMEs e 14 CACs. No estudo morfológico, foram analisados os subtipos histopatológicos dos APs (rico em células e pobre em células) (SOARES et al., 2009) e dos CACs (cribriforme, tubular e sólido) (ELLIS; AUCLAIR, 2008). De acordo com o grau histopatológico de malignidade, os CMEs foram classificados em: grau I, grau II e grau III (BRANDWEIN et al., 2001). No estudo imunoistoquímico, foram estabelecidos os percentuais de células neoplásicas positivas (citoplasma e núcleo) em 5 campos de maior imunorreatividade (400) aos anticorpos anti-Atg7, anti-LC3A, anti-p62 e anti-p-mTOR (OUYANG et al., 2017). Os dados obtidos foram analisados estatisticamente por meio dos testes de Mann-Whitney e de correlação de Spearman (p < 0,05). Foi constatada maior frequência de APs ricos em células (60,0%) e de CACs dos subtipos cribriforme (42,85%) e tubular (42,85%). Em relação ao grau histopatológico de malignidade dos CMEs, houve predomínio de casos com grau I (45,0%) e grau II (45,0%). Foi observada expressão citoplasmática de Atg7 em todos os grupos analisados, com altos percentuais medianos de positividade. Para LC3A, foi constatada imunopositividade citoplasmática na maioria dos ACPs (95,0%) e em todos os casos de AP, CME e CAC. Em relação à p62, os menores percentuais de expressão citoplasmática foram observados nos CACs e nos APs, ambos com diferença significativa quando comparados aos CMEs e ACPs (p < 0,05). Os maiores percentuais de expressão nuclear de p62 foram observados nos APs, com diferença estatisticamente significativa em comparação aos ACPs e CACs (p < 0,005). Os CACs apresentaram menores percentuais de positividade citoplasmática para p-mTOR quando comparados aos demais grupos de lesões (p < 0,005). Em relação à expressão nuclear de Atg7, LC3A e p-mTOR, todos os grupos apresentaram baixos percentuais de positividade. Não foram observadas diferenças estatisticamente significativas na imunoexpressão das proteínas relacionadas à autofagia de acordo com o subtipo histológico dos APs e CACs e o grau histopatológico de malignidade dos CMEs. Nos APs, CMEs e CACs, foram constatadas correlações positivas entre as imunoexpressões de proteínas relacionadas à autofagia (p < 0,05). Em conclusão, os resultados deste estudo sugerem um potencial envolvimento da autofagia na patogênese de APs, ACPs, CMEs e CACs de glândulas salivares. A regulação positiva da autofagia e a translocação nuclear reduzida da proteína p62 podem contribuir para o comportamento biológico agressivo do CAC de glândulas salivares.Submitted by Conluintes Doutorado (concluinte.doutorado@setor.uepb.edu.br) on 2021-06-10T00:12:50Z No. of bitstreams: 3 EMANUENE GALDINO PIRES (2).pdf: 4903943 bytes, checksum: 9a7a880245ebdc87ed1bb07f151da2d5 (MD5) TermoAutorizacao_TEDE_ EMANUENE GALDINO.pdf: 170675 bytes, checksum: 8578c2ea6a5a36e29092505b956a34fa (MD5) TermoCadastramento_BDTD__ EMANUENE GALDINO.pdf: 207328 bytes, checksum: b8faab64a6f04d51662e04ac2aa4021b (MD5)Rejected by Rosalvo Andrade (rosalvo_andrade@servidor.uepb.edu.br), reason: on 2021-06-10T01:24:32Z (GMT)Submitted by Conluintes Doutorado (concluinte.doutorado@setor.uepb.edu.br) on 2021-06-10T13:50:33Z No. of bitstreams: 3 EMANUENE GALDINO PIRES (2).pdf: 4903943 bytes, checksum: 9a7a880245ebdc87ed1bb07f151da2d5 (MD5) TermoAutorizacao_TEDE_Emanuene Galdino Pires.pdf: 88032 bytes, checksum: 12da3b721a454f121377b7819d0195c7 (MD5) TermoCadastramento_BDTD_Emanuene Galdino Pires.pdf: 117277 bytes, checksum: 89d97de6ffe7e7e8ce9e8816b16c1477 (MD5)Approved for entry into archive by Rosalvo Andrade (rosalvo_andrade@servidor.uepb.edu.br) on 2021-06-10T17:08:56Z (GMT) No. of bitstreams: 3 EMANUENE GALDINO PIRES (2).pdf: 4903943 bytes, checksum: 9a7a880245ebdc87ed1bb07f151da2d5 (MD5) TermoAutorizacao_TEDE_Emanuene Galdino Pires.pdf: 88032 bytes, checksum: 12da3b721a454f121377b7819d0195c7 (MD5) TermoCadastramento_BDTD_Emanuene Galdino Pires.pdf: 117277 bytes, checksum: 89d97de6ffe7e7e8ce9e8816b16c1477 (MD5)Made available in DSpace on 2021-11-24T23:35:14Z (GMT). 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dc.title.por.fl_str_mv |
Análise da imunoexpressão de proteínas relacionadas à autofagia (Atg7, LC3A, p62 e p-mTOR) em neoplasias de glândulas salivares |
title |
Análise da imunoexpressão de proteínas relacionadas à autofagia (Atg7, LC3A, p62 e p-mTOR) em neoplasias de glândulas salivares |
spellingShingle |
Análise da imunoexpressão de proteínas relacionadas à autofagia (Atg7, LC3A, p62 e p-mTOR) em neoplasias de glândulas salivares Pires, Emanuene Galdino Neoplasias das glândulas salivares Autofagia Imuno-histoquímica Salivary gland neoplasms Autophagy Immunohistochemistry ODONTOLOGIA::CLINICA ODONTOLOGICA |
title_short |
Análise da imunoexpressão de proteínas relacionadas à autofagia (Atg7, LC3A, p62 e p-mTOR) em neoplasias de glândulas salivares |
title_full |
Análise da imunoexpressão de proteínas relacionadas à autofagia (Atg7, LC3A, p62 e p-mTOR) em neoplasias de glândulas salivares |
title_fullStr |
Análise da imunoexpressão de proteínas relacionadas à autofagia (Atg7, LC3A, p62 e p-mTOR) em neoplasias de glândulas salivares |
title_full_unstemmed |
Análise da imunoexpressão de proteínas relacionadas à autofagia (Atg7, LC3A, p62 e p-mTOR) em neoplasias de glândulas salivares |
title_sort |
Análise da imunoexpressão de proteínas relacionadas à autofagia (Atg7, LC3A, p62 e p-mTOR) em neoplasias de glândulas salivares |
author |
Pires, Emanuene Galdino |
author_facet |
Pires, Emanuene Galdino |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Nonaka, Cassiano Francisco Weege |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/0224522010734716 |
dc.contributor.referee1.fl_str_mv |
Bonan, Paulo Rogério Ferreti |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/4201967424037508 |
dc.contributor.referee2.fl_str_mv |
Godoy, Gustavo Pina |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/5655149996985928 |
dc.contributor.referee3.fl_str_mv |
Costa, Edja Maria Melo de Brito |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/0192415370217147 |
dc.contributor.referee4.fl_str_mv |
Gordón-Núñez, Manuel Antonio |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/6553619409299152 |
dc.contributor.referee5.fl_str_mv |
Nonaka, Cassiano Francisco Weege |
dc.contributor.referee5Lattes.fl_str_mv |
http://lattes.cnpq.br/0224522010734716 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4390246107391803 |
dc.contributor.author.fl_str_mv |
Pires, Emanuene Galdino |
contributor_str_mv |
Nonaka, Cassiano Francisco Weege Bonan, Paulo Rogério Ferreti Godoy, Gustavo Pina Costa, Edja Maria Melo de Brito Gordón-Núñez, Manuel Antonio Nonaka, Cassiano Francisco Weege |
dc.subject.por.fl_str_mv |
Neoplasias das glândulas salivares Autofagia Imuno-histoquímica |
topic |
Neoplasias das glândulas salivares Autofagia Imuno-histoquímica Salivary gland neoplasms Autophagy Immunohistochemistry ODONTOLOGIA::CLINICA ODONTOLOGICA |
dc.subject.eng.fl_str_mv |
Salivary gland neoplasms Autophagy Immunohistochemistry |
dc.subject.cnpq.fl_str_mv |
ODONTOLOGIA::CLINICA ODONTOLOGICA |
description |
Pleomorphic adenoma (PA), polymorphous adenocarcinoma (PAC), mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are salivary gland neoplasms that exhibit important differences in their etiopathogenesis, histopathological characteristics and clinical behaviors. In the context of neoplastic development and progression, studies have highlighted the participation of an intracellular catabolic mechanism involved in physiological and pathological processes, denominated autophagy. This mechanism involves several molecules, with emphasis on Atg7, LC3, p62 and p-mTOR proteins. Investigations on autophagy in salivary gland neoplasms are recent and directed, especially, at ACC. In addition, these studies analyzed a small number of autophagy-related proteins, with emphasis on LC3 and mTOR. Thus, the objective of this study was to evaluate the immunoexpression of four autophagy-related proteins (Atg7, LC3A, p62 and p-mTOR) in PAs, PACs, MECs and ACCs of salivary glands. The sample consisted of 20 PAs, 20 PACs, 20 MECs and 14 ACCs. In the morphological study, the histopathological subtypes of PAs (cell-rich and cell-poor) (SOARES et al., 2009) and ACCs (cribriform, tubular and solid) (ELLIS; AUCLAIR, 2008) were analyzed. According to the histopathological grade of malignancy, MECs were classified as: grade I, grade II and grade III (BRANDWEIN et al., 2001). In the immunohistochemical study, the percentages of positive neoplastic cells (cytoplasm and nucleus) in 5 fields of highest immunoreactivity (400) for anti-Atg7, anti-LC3A, anti-p62 and anti-p-mTOR antibodies were determined (OUYANG et al., 2017). The data obtained were statistically analyzed using the Mann-Whitney test and Spearman’s correlation test (p < 0.05). There was a higher frequency of cell-rich PAs (60.0%) and cribriform (42.85%) and tubular (42.85%) ACCs. Regarding the histopathological grade of malignancy of MECs, there was a predominance of cases with grade I (45.0%) and grade II (45.0%). Cytoplasmic expression of Atg7 was observed in all groups analyzed, with high median percentages of positivity. For LC3A, cytoplasmic immunopositivity was found in most PACs (95.0%) and in all cases of PA, MEC and ACC. Regarding p62, the lowest percentages of cytoplasmic expression were observed in PAs and ACCs, both with significant difference compared to PACs and MECs (p < 0.05). The highest percentages of nuclear expression of p62 were observed in PAs, with statistically significant difference compared to PACs and ACCs (p < 0.005). ACCs showed lower percentages of cytoplasmic positivity for p-mTOR compared to other groups of lesions (p < 0.005). Regarding nuclear expression of Atg7, LC3A and p-mTOR, all groups exhibited low median percentages of positivity. There were no statistically significant differences in the immunoexpression of autophagy-related proteins according to the histopathological subtypes of PAs and ACCs and the histopathological grade of malignancy of MECs. In PAs, MECs and ACCs, positive correlations were observed between the immunoexpressions of autophagy-related proteins (p < 0.05). In conclusion, the results of this study suggest the potential involvement of autophagy in the pathogenesis of PA, PAC, CME and ACC of salivary glands. The upregulation of autophagy and the reduced nuclear translocation of protein p62 may contribute to aggressive biological behavior of ACC of salivary glands. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-12-09 |
dc.date.accessioned.fl_str_mv |
2021-11-24T23:35:14Z |
dc.date.available.fl_str_mv |
2021-12-09 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Pires, Emanuene Galdino. Análise da imunoexpressão de proteínas relacionadas à autofagia (Atg7, LC3A, p62 e p-mTOR) em neoplasias de glândulas salivares. 2020. 100p. Tese (Programa de Pós-Graduação em Odontologia - PPGO) - Universidade Estadual da Paraíba, Campina Grande. |
dc.identifier.uri.fl_str_mv |
http://tede.bc.uepb.edu.br/jspui/handle/tede/3861 |
identifier_str_mv |
Pires, Emanuene Galdino. Análise da imunoexpressão de proteínas relacionadas à autofagia (Atg7, LC3A, p62 e p-mTOR) em neoplasias de glândulas salivares. 2020. 100p. Tese (Programa de Pós-Graduação em Odontologia - PPGO) - Universidade Estadual da Paraíba, Campina Grande. |
url |
http://tede.bc.uepb.edu.br/jspui/handle/tede/3861 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
188746850794111162 |
dc.relation.confidence.fl_str_mv |
600 600 600 |
dc.relation.department.fl_str_mv |
524871450381110278 |
dc.relation.cnpq.fl_str_mv |
-1816740449898491657 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/embargoedAccess |
eu_rights_str_mv |
embargoedAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Estadual da Paraíba |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Odontologia - PPGO |
dc.publisher.initials.fl_str_mv |
UEPB |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Pró-Reitoria de Pós-Graduação e Pesquisa - PRPGP |
publisher.none.fl_str_mv |
Universidade Estadual da Paraíba |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UEPB instname:Universidade Estadual da Paraíba (UEPB) instacron:UEPB |
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Universidade Estadual da Paraíba (UEPB) |
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UEPB |
institution |
UEPB |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UEPB |
collection |
Biblioteca Digital de Teses e Dissertações da UEPB |
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http://tede.bc.uepb.edu.br/jspui/bitstream/tede/3861/5/license.txt http://tede.bc.uepb.edu.br/jspui/bitstream/tede/3861/2/EMANUENE+GALDINO+PIRES+%282%29.pdf http://tede.bc.uepb.edu.br/jspui/bitstream/tede/3861/6/TermoAutorizacao_TEDE_Emanuene+Galdino+Pires.pdf http://tede.bc.uepb.edu.br/jspui/bitstream/tede/3861/7/TermoCadastramento_BDTD_Emanuene+Galdino+Pires.pdf |
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Biblioteca Digital de Teses e Dissertações da UEPB - Universidade Estadual da Paraíba (UEPB) |
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bc@uepb.edu.br|| |
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