Imunoexpressão das proteínas efrina-A1 e efrina-B2 e dos receptores EphA1 e EphB4 em lesões periapicais primárias e persistentes

Detalhes bibliográficos
Ano de defesa: 2025
Autor(a) principal: Lima, Wliana Pontes de
Orientador(a): Gordón-Núñez, Manuel Antonio
Banca de defesa: Monteiro, Bárbara Vanessa de Brito, Pereira, Joabe dos Santos, Alves, Pollianna Muniz, Nonaka, Cassiano Francisco Weege, Gordón-Núñez, Manuel Antonio
Tipo de documento: Tese
Tipo de acesso: Acesso embargado
Idioma: por
Instituição de defesa: Universidade Estadual da Paraíba
Programa de Pós-Graduação: Programa de Pós-Graduação em Odontologia - PPGO
Departamento: Pró-Reitoria de Pós-Graduação e Pesquisa - PRPGP
País: BR
Palavras-chave em Português:
Palavras-chave em Inglês:
Área do conhecimento CNPq:
Link de acesso: https://repositorio.uepb.edu.br/handle/123456789/72011
Resumo: Endodontic treatment of periapical diseases shows a high rate of clinical success, however, in some cases, persistent periapical lesions (LP2) arise, which pose a challenge for Endodontics. In this context, it is essential to deepen the understanding of the pathogenesis of LP2, such as the study of the Eph/ephrin complex, since these proteins act in important biological processes for the development and persistence of LP. Thus, the present study aimed to evaluate, through immunohistochemistry, the expression of ephrin-A1, ephrin-B2 proteins and of the EphA1 and EphB4 receptors in cases of primary periapical lesions (LP1) and persistent. This is a descriptive and analytical laboratory study, in which 20 tissue samples of LP1 (10 periapical granulomas–GP and 10 radicular cysts–CR) and 20 LP2 (10 GP and 10 CR) were investigated. Cases of LP1 and LP2 were included, whose paraffin blocks were in good condition, contained sufficient material, and had properly completed clinical records. Cases without sufficient clinical and radiographic data to differentiate LP1 from LP2 were excluded. In addition, cases of LP2 without a prior history of non-surgical endodontic retreatment, without association with pain, edema, and the presence of a parulis were also excluded. Quantitative analysis of the immunohistochemical expression of ephrin-A1, ephrin B2 proteins and of the EphA1 and EphB4 receptors were performed after analysis of the clinical and morphological parameters and execution of the immunohistochemistry, using the immunoperoxidase method based on the dextran polymer technique. Areas of greatest immunoreactivity for ephrin-A1, ephrin-B2, EphA1, and EphB4 were selected and photomicrographed: five fields in the epithelium and five fields of the fibrous capsule of the CR, as well as five fields of the GP. Then, a count of immunopositive and negative cells was carried out, and the percentage of positivity was established. Subsequently, statistical analysis was performed using the SPSS software (version 25.0; USA), in which it was found that the sample did not show a normal distribution; therefore, non-parametric tests of Mann-Whitney and Kruskal-Wallis were applied, as well as Spearman's correlation test. A significance level of 5% (p<0,05) was considered for all tests. Cytoplasmic immunoexpression of ephrin-A1 was observed in all LP cases. The highest expressions of this protein occurred in CR2, with a statistically significant difference between the cytoplasmic immunoexpression of ephrin-A1 in the epithelium (p=0,002) and connective tissue (p=0,019) of CR2 when compared to CR1. GP1 showed a higher median percentage of positivity than GP2. Among the antibodies evaluated, EphA1 showed the highest medians of cytoplasmic and nuclear immunoexpression percentages, with higher expression in CR2, without statistically significant differences. Ephrin-B2 was expressed in the cytoplasm of all LP, with higher levels of immunoreactivity in the epithelium of CR2 and in the connective tissue of GP1. Nuclear expression of this protein was low in all LP. In turn, the EphB4 receptor showed greater immunoexpression in the epithelium of CR2 and in the connective tissue of CR1 and GP1. There was a statistically significant difference between the cytoplasmic immunoexpression of EphB4 in GP1 (p=0,001) when compared to GP2. Nuclear expression of this receptor was low, except in the epithelium of CR2. No statistically significant correlations were identified between the expressions of the evaluated proteins. Some of the evaluated proteins seem to influence the persistence of LP2, especially in CR2. On the other hand, the EphB4 receptor appears to play a protective role in LP1.
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spelling 2025-07-31T16:56:40Z2026-02-24T14:31:44Z2999-12-312025-06-26LIMA, Wliana Pontes de. Imunoexpressão das proteínas efrina-A1 e efrina-B2 e dos receptores EphA1 e EphB4 em lesões periapicais primárias e persistentes. 2025. 93 f. Tese (Doutorado em Odontologia) - Universidade Estadual da Paraíba, Campina Grande, 2025.https://repositorio.uepb.edu.br/handle/123456789/7201124004014010P2Endodontic treatment of periapical diseases shows a high rate of clinical success, however, in some cases, persistent periapical lesions (LP2) arise, which pose a challenge for Endodontics. In this context, it is essential to deepen the understanding of the pathogenesis of LP2, such as the study of the Eph/ephrin complex, since these proteins act in important biological processes for the development and persistence of LP. Thus, the present study aimed to evaluate, through immunohistochemistry, the expression of ephrin-A1, ephrin-B2 proteins and of the EphA1 and EphB4 receptors in cases of primary periapical lesions (LP1) and persistent. This is a descriptive and analytical laboratory study, in which 20 tissue samples of LP1 (10 periapical granulomas–GP and 10 radicular cysts–CR) and 20 LP2 (10 GP and 10 CR) were investigated. Cases of LP1 and LP2 were included, whose paraffin blocks were in good condition, contained sufficient material, and had properly completed clinical records. Cases without sufficient clinical and radiographic data to differentiate LP1 from LP2 were excluded. In addition, cases of LP2 without a prior history of non-surgical endodontic retreatment, without association with pain, edema, and the presence of a parulis were also excluded. Quantitative analysis of the immunohistochemical expression of ephrin-A1, ephrin B2 proteins and of the EphA1 and EphB4 receptors were performed after analysis of the clinical and morphological parameters and execution of the immunohistochemistry, using the immunoperoxidase method based on the dextran polymer technique. Areas of greatest immunoreactivity for ephrin-A1, ephrin-B2, EphA1, and EphB4 were selected and photomicrographed: five fields in the epithelium and five fields of the fibrous capsule of the CR, as well as five fields of the GP. Then, a count of immunopositive and negative cells was carried out, and the percentage of positivity was established. Subsequently, statistical analysis was performed using the SPSS software (version 25.0; USA), in which it was found that the sample did not show a normal distribution; therefore, non-parametric tests of Mann-Whitney and Kruskal-Wallis were applied, as well as Spearman's correlation test. A significance level of 5% (p<0,05) was considered for all tests. Cytoplasmic immunoexpression of ephrin-A1 was observed in all LP cases. The highest expressions of this protein occurred in CR2, with a statistically significant difference between the cytoplasmic immunoexpression of ephrin-A1 in the epithelium (p=0,002) and connective tissue (p=0,019) of CR2 when compared to CR1. GP1 showed a higher median percentage of positivity than GP2. Among the antibodies evaluated, EphA1 showed the highest medians of cytoplasmic and nuclear immunoexpression percentages, with higher expression in CR2, without statistically significant differences. Ephrin-B2 was expressed in the cytoplasm of all LP, with higher levels of immunoreactivity in the epithelium of CR2 and in the connective tissue of GP1. Nuclear expression of this protein was low in all LP. In turn, the EphB4 receptor showed greater immunoexpression in the epithelium of CR2 and in the connective tissue of CR1 and GP1. There was a statistically significant difference between the cytoplasmic immunoexpression of EphB4 in GP1 (p=0,001) when compared to GP2. Nuclear expression of this receptor was low, except in the epithelium of CR2. No statistically significant correlations were identified between the expressions of the evaluated proteins. Some of the evaluated proteins seem to influence the persistence of LP2, especially in CR2. On the other hand, the EphB4 receptor appears to play a protective role in LP1.O tratamento endodôntico das periapicopatias apresenta alta taxa de sucesso clínico, no entanto, em alguns casos, surgem as lesões periapicais persistentes (LP2), as quais configuram um desafio para a Endodontia. Nesse contexto, é essencial aprofundar a compreensão da patogênese das LP2, como o estudo do complexo Eph/efrina, pois tais proteínas atuam em processos biológicos importantes para o desenvolvimento e permanência das LP. Dessa forma, o presente estudo teve por objetivo avaliar, por meio da imunoistoquímica, a expressão das proteínas efrina-A1, efrina-B2 e dos receptores EphA1 e EphB4 em casos de lesões periapicais primárias (LP1) e persistentes. Trata-se de um estudo laboratorial, de caráter descritivo e analítico, no qual foram investigadas 20 amostras teciduais de LP1 (10 granulomas periapicais-GP e 10 cistos radiculares-CR) e 20 LP2 (10 GP e 10 CR). Foram incluídos casos de LP1 e LP2, cujos blocos parafinados estavam em bom estado, continham quantidade suficiente de material e apresentaram as fichas clínicas devidamente preenchidas. Foram excluídos os casos sem dados clínicos e radiográficos suficientes para diferenciar as LP1 das LP2. Além disso, os casos de LP2 sem histórico prévio de retratamento endodôntico não-cirúrgico, sem associação com dor, edema e presença de parúlide também foram excluídos. Foi realizada análise quantitativa da expressão imunoistoquímica das proteínas efrina-A1, efrina-B2 e dos receptores EphA1 e EphB4, após a análise dos parâmetros clínico morfológicos e da realização da imunoistoquímica, por meio do método da imunoperoxidase pela técnica baseada em polímeros de dextrano. Foram selecionadas e fotomicrografadas áreas de maior imunorreatividade para efrina-A1, efrina-B2, EphA1 e EphB4, cinco campos em epitélio e cinco campos da cápsula fibrosa dos CR, como também cinco campos dos GP. Em seguida, foi realizada a contagem de células imunopositivas e negativas, e estabelecido o percentual de positividade. Posteriormente, foi realizada a análise estatística, por meio do software SPSS (versão 25.0; USA), no qual foi verificado que a amostra não apresentou uma distribuição normal e por isso, foram aplicados os testes não-paramétricos de Mann-Whitney e de Kruskal-Wallis, bem como o teste de correlação de Spearman. Para todos os testes foi considerado o nível de significância de 5% (p<0,05). Foi observada imunoexpressão citoplasmática de efrina-A1 em todos os casos de LP. As maiores expressões dessa proteína ocorreram em CR2, com diferença estatisticamente significativa entre a imunoexpressão citoplasmática de efrina-A1 em epitélio (p=0,002) e conjuntivo (p=0,019) de CR2, quando comparado a CR1. Os GP1 apresentaram percentual mediano de positividade maior do que os GP2. Entre os anticorpos avaliados, EphA1 foi o que apresentou as maiores medianas dos percentuais de imunoexpressão citoplasmáticas e nucleares, com maior expressão em CR2, sem diferenças estatisticamente significativas. A efrina-B2 foi expressa no citoplasma de todas as LP, com maiores níveis de imunorreatividade no epitélio dos CR2 e no tecido conjuntivo dos GP1. A expressão nuclear dessa proteína foi baixa em todas as LP. Por sua vez, o receptor EphB4 apresentou maior imunoexpressão no epitélio dos CR2 e no tecido conjuntivo dos CR1 e GP1. Houve diferença estatisticamente significativa entre a imunoexpressão citoplasmática de EphB4 em GP1 (p=0,001), quando comparado aos GP2. A expressão nuclear desse receptor foi baixa, exceto no epitélio dos CR2. Não foram identificadas correlações estatisticamente significativas entre as expressões das proteínas avaliadas. Algumas das proteínas avaliadas parecem influenciar na persistência das LP2, especialmente nos CR2. Já o receptor EphB4 parece exercer um papel protetor nas LP1.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfUniversidade Estadual da ParaíbaPrograma de Pós-Graduação em Odontologia - PPGOUEPBBRPró-Reitoria de Pós-Graduação e Pesquisa - PRPGPEphrinsEph family receptorsRadicular cystPeriapical granulomaODONTOLOGIAEfrinasReceptores da família EphCisto radicularGranuloma periapicalImunoexpressão das proteínas efrina-A1 e efrina-B2 e dos receptores EphA1 e EphB4 em lesões periapicais primárias e persistentesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisMonteiro, Bárbara Vanessa de BritoPereira, Joabe dos SantosAlves, Pollianna MunizNonaka, Cassiano Francisco WeegeGordón-Núñez, Manuel AntonioGordón-Núñez, Manuel AntonioLima, Wliana Pontes deinfo:eu-repo/semantics/embargoedAccessporreponame:Repositório Institucional da Universidade Estadual da Paraíba (UEPB)instname:Universidade Estadual da Paraíba (UEPB)instacron:UEPBTHUMBNAILTS - Wliana Pontes de Lima.pdf.jpgTS - Wliana Pontes de Lima.pdf.jpgGenerated Thumbnailimage/jpeg3159https://repositorio.uepb.edu.br/bitstreams/04344722-4971-47cb-96f2-984d659a9bbd/download6b20a0a32595cd78d0f3b7b5af56ccecMD510falseAnonymousREAD2026-06-26Termo de Depósito BDTD.pdf.jpgTermo de Depósito BDTD.pdf.jpgGenerated Thumbnailimage/jpeg4628https://repositorio.uepb.edu.br/bitstreams/cd5bf8b6-8d36-4372-8a25-4920d649fb09/download339d1edd086b53d9047ae89b28506aa1MD511falseAdministratorREAD2999-12-31LICENSElicense.txtlicense.txttext/plain; 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dc.title.none.fl_str_mv Imunoexpressão das proteínas efrina-A1 e efrina-B2 e dos receptores EphA1 e EphB4 em lesões periapicais primárias e persistentes
title Imunoexpressão das proteínas efrina-A1 e efrina-B2 e dos receptores EphA1 e EphB4 em lesões periapicais primárias e persistentes
spellingShingle Imunoexpressão das proteínas efrina-A1 e efrina-B2 e dos receptores EphA1 e EphB4 em lesões periapicais primárias e persistentes
Lima, Wliana Pontes de
Ephrins
Eph family receptors
Radicular cyst
Periapical granuloma
ODONTOLOGIA
Efrinas
Receptores da família Eph
Cisto radicular
Granuloma periapical
title_short Imunoexpressão das proteínas efrina-A1 e efrina-B2 e dos receptores EphA1 e EphB4 em lesões periapicais primárias e persistentes
title_full Imunoexpressão das proteínas efrina-A1 e efrina-B2 e dos receptores EphA1 e EphB4 em lesões periapicais primárias e persistentes
title_fullStr Imunoexpressão das proteínas efrina-A1 e efrina-B2 e dos receptores EphA1 e EphB4 em lesões periapicais primárias e persistentes
title_full_unstemmed Imunoexpressão das proteínas efrina-A1 e efrina-B2 e dos receptores EphA1 e EphB4 em lesões periapicais primárias e persistentes
title_sort Imunoexpressão das proteínas efrina-A1 e efrina-B2 e dos receptores EphA1 e EphB4 em lesões periapicais primárias e persistentes
author Lima, Wliana Pontes de
author_facet Lima, Wliana Pontes de
author_role author
dc.contributor.referee1.fl_str_mv Monteiro, Bárbara Vanessa de Brito
dc.contributor.referee2.fl_str_mv Pereira, Joabe dos Santos
dc.contributor.referee3.fl_str_mv Alves, Pollianna Muniz
dc.contributor.referee4.fl_str_mv Nonaka, Cassiano Francisco Weege
dc.contributor.referee5.fl_str_mv Gordón-Núñez, Manuel Antonio
dc.contributor.advisor1.fl_str_mv Gordón-Núñez, Manuel Antonio
dc.contributor.author.fl_str_mv Lima, Wliana Pontes de
contributor_str_mv Monteiro, Bárbara Vanessa de Brito
Pereira, Joabe dos Santos
Alves, Pollianna Muniz
Nonaka, Cassiano Francisco Weege
Gordón-Núñez, Manuel Antonio
Gordón-Núñez, Manuel Antonio
dc.subject.eng.fl_str_mv Ephrins
Eph family receptors
Radicular cyst
Periapical granuloma
topic Ephrins
Eph family receptors
Radicular cyst
Periapical granuloma
ODONTOLOGIA
Efrinas
Receptores da família Eph
Cisto radicular
Granuloma periapical
dc.subject.cnpq.fl_str_mv ODONTOLOGIA
dc.subject.por.fl_str_mv Efrinas
Receptores da família Eph
Cisto radicular
Granuloma periapical
description Endodontic treatment of periapical diseases shows a high rate of clinical success, however, in some cases, persistent periapical lesions (LP2) arise, which pose a challenge for Endodontics. In this context, it is essential to deepen the understanding of the pathogenesis of LP2, such as the study of the Eph/ephrin complex, since these proteins act in important biological processes for the development and persistence of LP. Thus, the present study aimed to evaluate, through immunohistochemistry, the expression of ephrin-A1, ephrin-B2 proteins and of the EphA1 and EphB4 receptors in cases of primary periapical lesions (LP1) and persistent. This is a descriptive and analytical laboratory study, in which 20 tissue samples of LP1 (10 periapical granulomas–GP and 10 radicular cysts–CR) and 20 LP2 (10 GP and 10 CR) were investigated. Cases of LP1 and LP2 were included, whose paraffin blocks were in good condition, contained sufficient material, and had properly completed clinical records. Cases without sufficient clinical and radiographic data to differentiate LP1 from LP2 were excluded. In addition, cases of LP2 without a prior history of non-surgical endodontic retreatment, without association with pain, edema, and the presence of a parulis were also excluded. Quantitative analysis of the immunohistochemical expression of ephrin-A1, ephrin B2 proteins and of the EphA1 and EphB4 receptors were performed after analysis of the clinical and morphological parameters and execution of the immunohistochemistry, using the immunoperoxidase method based on the dextran polymer technique. Areas of greatest immunoreactivity for ephrin-A1, ephrin-B2, EphA1, and EphB4 were selected and photomicrographed: five fields in the epithelium and five fields of the fibrous capsule of the CR, as well as five fields of the GP. Then, a count of immunopositive and negative cells was carried out, and the percentage of positivity was established. Subsequently, statistical analysis was performed using the SPSS software (version 25.0; USA), in which it was found that the sample did not show a normal distribution; therefore, non-parametric tests of Mann-Whitney and Kruskal-Wallis were applied, as well as Spearman's correlation test. A significance level of 5% (p<0,05) was considered for all tests. Cytoplasmic immunoexpression of ephrin-A1 was observed in all LP cases. The highest expressions of this protein occurred in CR2, with a statistically significant difference between the cytoplasmic immunoexpression of ephrin-A1 in the epithelium (p=0,002) and connective tissue (p=0,019) of CR2 when compared to CR1. GP1 showed a higher median percentage of positivity than GP2. Among the antibodies evaluated, EphA1 showed the highest medians of cytoplasmic and nuclear immunoexpression percentages, with higher expression in CR2, without statistically significant differences. Ephrin-B2 was expressed in the cytoplasm of all LP, with higher levels of immunoreactivity in the epithelium of CR2 and in the connective tissue of GP1. Nuclear expression of this protein was low in all LP. In turn, the EphB4 receptor showed greater immunoexpression in the epithelium of CR2 and in the connective tissue of CR1 and GP1. There was a statistically significant difference between the cytoplasmic immunoexpression of EphB4 in GP1 (p=0,001) when compared to GP2. Nuclear expression of this receptor was low, except in the epithelium of CR2. No statistically significant correlations were identified between the expressions of the evaluated proteins. Some of the evaluated proteins seem to influence the persistence of LP2, especially in CR2. On the other hand, the EphB4 receptor appears to play a protective role in LP1.
publishDate 2025
dc.date.accessioned.fl_str_mv 2025-07-31T16:56:40Z
2026-02-24T14:31:44Z
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dc.identifier.citation.fl_str_mv LIMA, Wliana Pontes de. Imunoexpressão das proteínas efrina-A1 e efrina-B2 e dos receptores EphA1 e EphB4 em lesões periapicais primárias e persistentes. 2025. 93 f. Tese (Doutorado em Odontologia) - Universidade Estadual da Paraíba, Campina Grande, 2025.
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identifier_str_mv LIMA, Wliana Pontes de. Imunoexpressão das proteínas efrina-A1 e efrina-B2 e dos receptores EphA1 e EphB4 em lesões periapicais primárias e persistentes. 2025. 93 f. Tese (Doutorado em Odontologia) - Universidade Estadual da Paraíba, Campina Grande, 2025.
24004014010P2
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