Imunoexpressão da quimiocina CXCL12 e seu receptor CXCR4 em carcinomas adenoides císticos de glândulas salivares

Detalhes bibliográficos
Autor(a) principal: Lucena, Amanda Lira Rufino de
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UEPB
Texto Completo: http://tede.bc.uepb.edu.br/jspui/handle/tede/3223
Resumo: Cystic adenoid carcinoma (ACC) is a malignant tumor of epithelial origin, with an unpredictable clinical course and its pathogenesis is not well understood. The interaction of the CXCL12 (SDF-1) chemokine with its CXCR4 (CD184) receptor induces, through several pathways, important intracellular signaling in neoplastic pathogenesis, regulating events such as proliferation, differentiation, apoptosis, chemotaxis and metastasis. The CXCL12/CXCR4 complex has been associated with several events associated with malignant tumor progression in humans, but little is known about its role in malignant salivary gland neoplasm. The objective of this study was to analyze the immunohistochemical expression of CXCL12 / CXCR4 in cystic adenoid carcinomas of the salivary glands, related to histopathological parameters, aiming to obtain information about the role of such proteins in the pathogenesis, biological behavior and prognosis of this neoplasm. Through the immunocytochemistry, the intratumoral, peritumoral and antibody positive indexes were investigated against CXCL12 and CXCR4 and analyzed in relation to histomorphological parameters characterized by the WHO histopathological classification system and the system of histopathological grading of malignancy proposed by van Weert et al in 17 CAC. Were evaluated 17 ACCs with predominance of the tubular histopathological pattern and cases of high histopathological grade of malignancy. There was a trend towards higher expression of CXCL12 in the intratumoral region of the cribriform pattern and in the peritumoral region of the solid pattern. The general IP of expression of CXCL12 was similar in histopathological patterns. A statistically significant difference was observed for the intratumoral expression of CXCL12 (p = 0.005) and general index of expression (p = 0.009). There was a significant association of the intratumoral expression of CXCL12 in relation to the degree of malignancy, especially in low grade cases (p = 0.005). The general index expression of CXCL12 was significantly associated with the histopathological grade of malignancy (p = 0.009). There was a tendency for greater expression of CXCR4 in the intratumoral and peritumoral region of the tubular pattern. The general index of expression of CXCR4 tended to decrease in solid, cribriform and tubular patterns. There was no significant association of intratumoral, peritumoral and general expression of CXCR4 in relation to the histopathological grade of malignancy of the sample. There was no statistically significant correlation between the expression of CXCL12 and CXCR4 in the tumor regions evaluated in both the low and high histological grade of malignancy. It was concluded that the immunoexpression of CXCL12 and CXCR4 in salivary glandular cystic adenoid carcinoma is practically equivalent in the intratumoral and peritumoral regions. However, considering the histological subtypes of CAC evaluated here, there was a trend towards greater immunoexpression of the chemokine in the intratumoral region, suggesting some role of this chemokine in the regulation of the mechanisms that guarantees the proliferation and maintenance of neoplastic cell viability when interacting with the CXCR4 receptor that was strongly expressed in all tumor regions. In addition, this receptor would also be, in turn, making the neoplastic cells apt to invade and / or metastasize.
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spelling Górdon-Nunes, Manuel Antônio97866326497Nonaka, Cassiano Francisco Weege02781932426Queiroz, Lélia Maria Guedes5953922442009009128474http://lattes.cnpq.br/4921309246156932Lucena, Amanda Lira Rufino de2019-03-21T19:27:49Z2018-07-18LUCENA, A. L. R. de. Imunoexpressão da quimiocina CXCL12 e seu receptor CXCR4 em carcinomas adenoides císticos de glândulas salivares. 2018. 93f. Dissertação (Programa de Pós-Graduação em Odontologia - PPGO) - Universidade Estadual da Paraíba, Campina Grande, 2018.http://tede.bc.uepb.edu.br/jspui/handle/tede/3223Cystic adenoid carcinoma (ACC) is a malignant tumor of epithelial origin, with an unpredictable clinical course and its pathogenesis is not well understood. The interaction of the CXCL12 (SDF-1) chemokine with its CXCR4 (CD184) receptor induces, through several pathways, important intracellular signaling in neoplastic pathogenesis, regulating events such as proliferation, differentiation, apoptosis, chemotaxis and metastasis. The CXCL12/CXCR4 complex has been associated with several events associated with malignant tumor progression in humans, but little is known about its role in malignant salivary gland neoplasm. The objective of this study was to analyze the immunohistochemical expression of CXCL12 / CXCR4 in cystic adenoid carcinomas of the salivary glands, related to histopathological parameters, aiming to obtain information about the role of such proteins in the pathogenesis, biological behavior and prognosis of this neoplasm. Through the immunocytochemistry, the intratumoral, peritumoral and antibody positive indexes were investigated against CXCL12 and CXCR4 and analyzed in relation to histomorphological parameters characterized by the WHO histopathological classification system and the system of histopathological grading of malignancy proposed by van Weert et al in 17 CAC. Were evaluated 17 ACCs with predominance of the tubular histopathological pattern and cases of high histopathological grade of malignancy. There was a trend towards higher expression of CXCL12 in the intratumoral region of the cribriform pattern and in the peritumoral region of the solid pattern. The general IP of expression of CXCL12 was similar in histopathological patterns. A statistically significant difference was observed for the intratumoral expression of CXCL12 (p = 0.005) and general index of expression (p = 0.009). There was a significant association of the intratumoral expression of CXCL12 in relation to the degree of malignancy, especially in low grade cases (p = 0.005). The general index expression of CXCL12 was significantly associated with the histopathological grade of malignancy (p = 0.009). There was a tendency for greater expression of CXCR4 in the intratumoral and peritumoral region of the tubular pattern. The general index of expression of CXCR4 tended to decrease in solid, cribriform and tubular patterns. There was no significant association of intratumoral, peritumoral and general expression of CXCR4 in relation to the histopathological grade of malignancy of the sample. There was no statistically significant correlation between the expression of CXCL12 and CXCR4 in the tumor regions evaluated in both the low and high histological grade of malignancy. It was concluded that the immunoexpression of CXCL12 and CXCR4 in salivary glandular cystic adenoid carcinoma is practically equivalent in the intratumoral and peritumoral regions. However, considering the histological subtypes of CAC evaluated here, there was a trend towards greater immunoexpression of the chemokine in the intratumoral region, suggesting some role of this chemokine in the regulation of the mechanisms that guarantees the proliferation and maintenance of neoplastic cell viability when interacting with the CXCR4 receptor that was strongly expressed in all tumor regions. In addition, this receptor would also be, in turn, making the neoplastic cells apt to invade and / or metastasize.O carcinoma adenoide cístico (CAC) é um tumor maligno de origem epitelial, com curso clínico imprevisível, cuja patogenia ainda não é bem esclarecida. A interação da quimiocina CXCL12 (SDF-1) com o seu receptor CXCR4 (CD184) induz sinalizações intracelulares importantes na patogenia neoplásica, regulando a proliferação, differenciação, apoptose, quimiotaxia e metástase celulares. O complexo CXCL12/CXCR4 tem sido associado a diversos eventos associados à progressão tumoral maligna em humanos, porém pouco se conhece do seu papel em neoplasias malignas de glândulas salivares. Objetivou-se analisar a expressão imunoistoquímica da CXCL12/CXCR4 em carcinomas adenoides císticos de glândulas salivares relacionando-a com parâmetros histopatológicos. Foram pesquisados os índices de positividade (IP) intratumoral, peritumoral e geral de anticorpos contra CXCL12 e CXCR4 e analisada em relação a parâmetros histomorfológicos caracterizados através do sistema de classificação histopatológica da OMS e o sistema de gradação histopatológica de malignidade proposto por van Weert et al em 17 CAC. Foram avaliados 17 CAC com predominância do padrão histopatológico tubular e casos de alto grau histopatológico de malignidade. Houve tendência a maior IP de expressão de CXCL12 na região intratumoral do padrão cribriforme e na região peritumoral do padrão sólido. O IP geral de expressão da CXCL12 foi semelhante nos padrões histopatológicos. Observou-se diferença estatisticamente significativa do IP de CXCL12 intratumoral (p=0,005) e do IP geral (p=0,009). Verificou-se associação significativa do IP intratumoral de CXCL12 em relação ao grau de malignidade, principalmente em casos de baixo grau (p=0,005). O IP geral da quimiocina teve associação significativa com o grau histopatológico de malignidade (p=0,009). Houve tendência a maior expressão de CXCR4 na região intratumoral e peritumoral do padrão tubular. O IP geral de CXCR4 tendeu a decrescer nos padrões sólido, cribriforme e tubular. Não houve associação significativa do IP de CXCR4 das regiões avaliadas em relação ao grau histopatológico de malignidade. Não houve correlação estatisticamente significativa da expressão de CXCL12 e CXCR4 nas regiões tumorais no baixo e alto grau histológico de malignidade. Conclui-se que a imunoexpressão de CXCL12 e de CXCR4 em carcinoma adenoide cístico glandular salivar é praticamente equivalente na região intratumoral e na peritumoral. Porém considerando os subtipos histológicos do CAC, a tendência a maior imunoexpressão da quimiocina na região intratumoral sugere algum papel dessa quimiocina na regulação dos mecanismos que garantem a proliferação e manutenção da viabilidade celular neoplásica ao interagir com o receptor CXCR4 que foi fortemente expresso em todas as regiões tumorais. Além disso, esse receptor também estaria, por sua vez, tornando as células neoplásicas aptas para invadir e/ou metastatizar.Submitted by Jean Medeiros (jeanletras@uepb.edu.br) on 2019-02-28T14:13:39Z No. of bitstreams: 1 PDF - Amanda Lira Rufino de Lucena.pdf: 21152348 bytes, checksum: 0956d8c1ebbac3c0fee81a0cc1528a41 (MD5)Approved for entry into archive by Secta BC (secta.csu.bc@uepb.edu.br) on 2019-03-21T19:27:49Z (GMT) No. of bitstreams: 1 PDF - Amanda Lira Rufino de Lucena.pdf: 21152348 bytes, checksum: 0956d8c1ebbac3c0fee81a0cc1528a41 (MD5)Made available in DSpace on 2019-03-21T19:27:49Z (GMT). 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dc.title.por.fl_str_mv Imunoexpressão da quimiocina CXCL12 e seu receptor CXCR4 em carcinomas adenoides císticos de glândulas salivares
title Imunoexpressão da quimiocina CXCL12 e seu receptor CXCR4 em carcinomas adenoides císticos de glândulas salivares
spellingShingle Imunoexpressão da quimiocina CXCL12 e seu receptor CXCR4 em carcinomas adenoides císticos de glândulas salivares
Lucena, Amanda Lira Rufino de
CXCL12
CXCR4
Neoplasia
Glândula salivar
Carcinoma adenoide cístico
Neoplasm
Cystic adenoid carcinoma
Salivary Gland
CIENCIAS DA SAUDE::ODONTOLOGIA
title_short Imunoexpressão da quimiocina CXCL12 e seu receptor CXCR4 em carcinomas adenoides císticos de glândulas salivares
title_full Imunoexpressão da quimiocina CXCL12 e seu receptor CXCR4 em carcinomas adenoides císticos de glândulas salivares
title_fullStr Imunoexpressão da quimiocina CXCL12 e seu receptor CXCR4 em carcinomas adenoides císticos de glândulas salivares
title_full_unstemmed Imunoexpressão da quimiocina CXCL12 e seu receptor CXCR4 em carcinomas adenoides císticos de glândulas salivares
title_sort Imunoexpressão da quimiocina CXCL12 e seu receptor CXCR4 em carcinomas adenoides císticos de glândulas salivares
author Lucena, Amanda Lira Rufino de
author_facet Lucena, Amanda Lira Rufino de
author_role author
dc.contributor.advisor1.fl_str_mv Górdon-Nunes, Manuel Antônio
dc.contributor.advisor1ID.fl_str_mv 97866326497
dc.contributor.referee1.fl_str_mv Nonaka, Cassiano Francisco Weege
dc.contributor.referee1ID.fl_str_mv 02781932426
dc.contributor.referee2.fl_str_mv Queiroz, Lélia Maria Guedes
dc.contributor.referee2ID.fl_str_mv 59539224420
dc.contributor.authorID.fl_str_mv 09009128474
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/4921309246156932
dc.contributor.author.fl_str_mv Lucena, Amanda Lira Rufino de
contributor_str_mv Górdon-Nunes, Manuel Antônio
Nonaka, Cassiano Francisco Weege
Queiroz, Lélia Maria Guedes
dc.subject.por.fl_str_mv CXCL12
CXCR4
Neoplasia
Glândula salivar
Carcinoma adenoide cístico
topic CXCL12
CXCR4
Neoplasia
Glândula salivar
Carcinoma adenoide cístico
Neoplasm
Cystic adenoid carcinoma
Salivary Gland
CIENCIAS DA SAUDE::ODONTOLOGIA
dc.subject.eng.fl_str_mv Neoplasm
Cystic adenoid carcinoma
Salivary Gland
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::ODONTOLOGIA
description Cystic adenoid carcinoma (ACC) is a malignant tumor of epithelial origin, with an unpredictable clinical course and its pathogenesis is not well understood. The interaction of the CXCL12 (SDF-1) chemokine with its CXCR4 (CD184) receptor induces, through several pathways, important intracellular signaling in neoplastic pathogenesis, regulating events such as proliferation, differentiation, apoptosis, chemotaxis and metastasis. The CXCL12/CXCR4 complex has been associated with several events associated with malignant tumor progression in humans, but little is known about its role in malignant salivary gland neoplasm. The objective of this study was to analyze the immunohistochemical expression of CXCL12 / CXCR4 in cystic adenoid carcinomas of the salivary glands, related to histopathological parameters, aiming to obtain information about the role of such proteins in the pathogenesis, biological behavior and prognosis of this neoplasm. Through the immunocytochemistry, the intratumoral, peritumoral and antibody positive indexes were investigated against CXCL12 and CXCR4 and analyzed in relation to histomorphological parameters characterized by the WHO histopathological classification system and the system of histopathological grading of malignancy proposed by van Weert et al in 17 CAC. Were evaluated 17 ACCs with predominance of the tubular histopathological pattern and cases of high histopathological grade of malignancy. There was a trend towards higher expression of CXCL12 in the intratumoral region of the cribriform pattern and in the peritumoral region of the solid pattern. The general IP of expression of CXCL12 was similar in histopathological patterns. A statistically significant difference was observed for the intratumoral expression of CXCL12 (p = 0.005) and general index of expression (p = 0.009). There was a significant association of the intratumoral expression of CXCL12 in relation to the degree of malignancy, especially in low grade cases (p = 0.005). The general index expression of CXCL12 was significantly associated with the histopathological grade of malignancy (p = 0.009). There was a tendency for greater expression of CXCR4 in the intratumoral and peritumoral region of the tubular pattern. The general index of expression of CXCR4 tended to decrease in solid, cribriform and tubular patterns. There was no significant association of intratumoral, peritumoral and general expression of CXCR4 in relation to the histopathological grade of malignancy of the sample. There was no statistically significant correlation between the expression of CXCL12 and CXCR4 in the tumor regions evaluated in both the low and high histological grade of malignancy. It was concluded that the immunoexpression of CXCL12 and CXCR4 in salivary glandular cystic adenoid carcinoma is practically equivalent in the intratumoral and peritumoral regions. However, considering the histological subtypes of CAC evaluated here, there was a trend towards greater immunoexpression of the chemokine in the intratumoral region, suggesting some role of this chemokine in the regulation of the mechanisms that guarantees the proliferation and maintenance of neoplastic cell viability when interacting with the CXCR4 receptor that was strongly expressed in all tumor regions. In addition, this receptor would also be, in turn, making the neoplastic cells apt to invade and / or metastasize.
publishDate 2018
dc.date.issued.fl_str_mv 2018-07-18
dc.date.accessioned.fl_str_mv 2019-03-21T19:27:49Z
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dc.identifier.citation.fl_str_mv LUCENA, A. L. R. de. Imunoexpressão da quimiocina CXCL12 e seu receptor CXCR4 em carcinomas adenoides císticos de glândulas salivares. 2018. 93f. Dissertação (Programa de Pós-Graduação em Odontologia - PPGO) - Universidade Estadual da Paraíba, Campina Grande, 2018.
dc.identifier.uri.fl_str_mv http://tede.bc.uepb.edu.br/jspui/handle/tede/3223
identifier_str_mv LUCENA, A. L. R. de. Imunoexpressão da quimiocina CXCL12 e seu receptor CXCR4 em carcinomas adenoides císticos de glândulas salivares. 2018. 93f. Dissertação (Programa de Pós-Graduação em Odontologia - PPGO) - Universidade Estadual da Paraíba, Campina Grande, 2018.
url http://tede.bc.uepb.edu.br/jspui/handle/tede/3223
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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
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repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da UEPB - Universidade Estadual da Paraíba (UEPB)
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