Imunoexpressão das proteínas E-caderina, α-SMA, TGF-β e Snail em queilites actínicas e carcinoma epidermoide de lábio inferior

Epithelial-mesenchymal transition (EMT) is a biological process that has been widely studied in oral squamous cell carcinoma (SCC), however, it is still rarely evaluated in lip carcinogenesis. The aim of this study was to investigate the immunoexpression of E-cadherin, α-SMA, TGF-β and Snail prot...

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Autor principal: Morais, Hannah Gil de Farias
Outros Autores: Freitas, Roseana de Almeida
Formato: Dissertação
Idioma:pt_BR
Publicado em: Universidade Federal do Rio Grande do Norte
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Endereço do item:https://repositorio.ufrn.br/handle/123456789/33126
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id ri-123456789-33126
record_format dspace
institution Repositório Institucional
collection RI - UFRN
language pt_BR
topic Carcinoma de células escamosas
Câncer oral
Transição epitéliomesenquimal
Prognóstico
spellingShingle Carcinoma de células escamosas
Câncer oral
Transição epitéliomesenquimal
Prognóstico
Morais, Hannah Gil de Farias
Imunoexpressão das proteínas E-caderina, α-SMA, TGF-β e Snail em queilites actínicas e carcinoma epidermoide de lábio inferior
description Epithelial-mesenchymal transition (EMT) is a biological process that has been widely studied in oral squamous cell carcinoma (SCC), however, it is still rarely evaluated in lip carcinogenesis. The aim of this study was to investigate the immunoexpression of E-cadherin, α-SMA, TGF-β and Snail proteins in actinic cheilitis (AC) histopathologically diagnosed as epithelial dysplasia, and in lower lip squamous cell carcinoma (LLSCC). The immunoexpression of E-cadherin, α-SMA, TGF-β and Snail was semiquantitatively analyzed in 54 cases of ACs and 49 LLSCCs. Aiming at association of immunohistochemical findings with clinicopathological variables and overall (OS) and disease-free (DFS) survival rates, cases were classified into low expression and high expression categories. There were no statistically significant associations with any of the proteins analyzed with the degree of severity of epithelial dysplasia in ACs (p > 0.05). Immunohistochemical analysis in LLSCCs revealed that low membrane expression of E-cadherin in tumor front was significantly associated with LLSCCs with ≥5 buds (p = 0.005) and high score for both BD model (p = 0.009) and the proposed model by Dourado et al. (2020) (p = 0.038), however, no significant associations were observed between immunoexpression of this protein and clinical parameters (p > 0.05). Significant associations were also found between low expression of α-SMA with LLSCCs in clinical stages TNM I/II (p = 0.05), low depth of invasion (p = 0.006), < 5 buds (p = 0.027) and score of low/intermediate risk, while high expression of this protein was associated with the outcome of death (p = 0.009). Significant associations were also found between α-SMA network/spindle immunostaining pattern with LLSCCs in TNM stages III/IV (p = 0.031), with high depth of invasion (p = 0.002), ≥5 buds (p = 0.027), high BD risk score (p = 0.001) and death outcome (p = 0.015). Regarding the TGF-β protein, statistically significant associations were noticed between its low expression in tumor buds with absence of lymph node metastasis (p = 0.047) and locoregional recurrence (p = 0.042), however, no significance was observed with any of morphological parameters (p > 0.05). Immunohistochemical analysis of Snail protein did not reveal any significant association with clinicopathological parameters (p > 0.05). The association analysis of protein immunoexpression between the lesions studied revealed significant results for a high cytoplasmic expression of E-cadherin and LLSCCs (p = 0.001), high expression of α-SMA and LLSCCs (p < 0.001), low expression of TGF -β and LLSCCs (p < 0.001) and high expression of Snail and ACs (p = 0.006). Survival analysis revealed a high expression of α-SMA in tumor front stroma (p = 0.013), a network immunostaining pattern of this protein (p = 0.046) and high expression of TGF-β in tumor buds (p = 0.043) were significantly associated with worse OS, and LLSCCs with high expression of α-SMA also had a higher risk of death (HR = 5.90, p = 0.030). High cytoplasmic expression of TGF-β in tumor buds was significantly associated with both worse DFS (p = 0.007) and higher risks of negative outcomes for DFS (HR = 4.44; p = 0.014). The results of present study suggest that although the immunoexpression of evaluated proteins does not indicate differences in degree of histopathological severity in ACs, dysregulations of these proteins were identified among the lesions studied. Furthermore, it was found that LLSCC with more aggressive behavior was associated with low expression of membrane E-cadherin, high expression of α-SMA and its network pattern, and low expression of TGF-β in tumor buds.
author2 Freitas, Roseana de Almeida
author_facet Freitas, Roseana de Almeida
Morais, Hannah Gil de Farias
format masterThesis
author Morais, Hannah Gil de Farias
author_sort Morais, Hannah Gil de Farias
title Imunoexpressão das proteínas E-caderina, α-SMA, TGF-β e Snail em queilites actínicas e carcinoma epidermoide de lábio inferior
title_short Imunoexpressão das proteínas E-caderina, α-SMA, TGF-β e Snail em queilites actínicas e carcinoma epidermoide de lábio inferior
title_full Imunoexpressão das proteínas E-caderina, α-SMA, TGF-β e Snail em queilites actínicas e carcinoma epidermoide de lábio inferior
title_fullStr Imunoexpressão das proteínas E-caderina, α-SMA, TGF-β e Snail em queilites actínicas e carcinoma epidermoide de lábio inferior
title_full_unstemmed Imunoexpressão das proteínas E-caderina, α-SMA, TGF-β e Snail em queilites actínicas e carcinoma epidermoide de lábio inferior
title_sort imunoexpressão das proteínas e-caderina, α-sma, tgf-β e snail em queilites actínicas e carcinoma epidermoide de lábio inferior
publisher Universidade Federal do Rio Grande do Norte
publishDate 2021
url https://repositorio.ufrn.br/handle/123456789/33126
work_keys_str_mv AT moraishannahgildefarias imunoexpressaodasproteinasecaderinaasmatgfbesnailemqueilitesactinicasecarcinomaepidermoidedelabioinferior
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spelling ri-123456789-331262021-08-13T16:03:18Z Imunoexpressão das proteínas E-caderina, α-SMA, TGF-β e Snail em queilites actínicas e carcinoma epidermoide de lábio inferior Morais, Hannah Gil de Farias Freitas, Roseana de Almeida http://lattes.cnpq.br/2116887315092579 http://lattes.cnpq.br/9512014003639405 Silveira, Ericka Janine Dantas da http://lattes.cnpq.br/2186658404241838 Santos, Hellen Bandeira de Pontes http://lattes.cnpq.br/1903543753108418 Carcinoma de células escamosas Câncer oral Transição epitéliomesenquimal Prognóstico Epithelial-mesenchymal transition (EMT) is a biological process that has been widely studied in oral squamous cell carcinoma (SCC), however, it is still rarely evaluated in lip carcinogenesis. The aim of this study was to investigate the immunoexpression of E-cadherin, α-SMA, TGF-β and Snail proteins in actinic cheilitis (AC) histopathologically diagnosed as epithelial dysplasia, and in lower lip squamous cell carcinoma (LLSCC). The immunoexpression of E-cadherin, α-SMA, TGF-β and Snail was semiquantitatively analyzed in 54 cases of ACs and 49 LLSCCs. Aiming at association of immunohistochemical findings with clinicopathological variables and overall (OS) and disease-free (DFS) survival rates, cases were classified into low expression and high expression categories. There were no statistically significant associations with any of the proteins analyzed with the degree of severity of epithelial dysplasia in ACs (p > 0.05). Immunohistochemical analysis in LLSCCs revealed that low membrane expression of E-cadherin in tumor front was significantly associated with LLSCCs with ≥5 buds (p = 0.005) and high score for both BD model (p = 0.009) and the proposed model by Dourado et al. (2020) (p = 0.038), however, no significant associations were observed between immunoexpression of this protein and clinical parameters (p > 0.05). Significant associations were also found between low expression of α-SMA with LLSCCs in clinical stages TNM I/II (p = 0.05), low depth of invasion (p = 0.006), < 5 buds (p = 0.027) and score of low/intermediate risk, while high expression of this protein was associated with the outcome of death (p = 0.009). Significant associations were also found between α-SMA network/spindle immunostaining pattern with LLSCCs in TNM stages III/IV (p = 0.031), with high depth of invasion (p = 0.002), ≥5 buds (p = 0.027), high BD risk score (p = 0.001) and death outcome (p = 0.015). Regarding the TGF-β protein, statistically significant associations were noticed between its low expression in tumor buds with absence of lymph node metastasis (p = 0.047) and locoregional recurrence (p = 0.042), however, no significance was observed with any of morphological parameters (p > 0.05). Immunohistochemical analysis of Snail protein did not reveal any significant association with clinicopathological parameters (p > 0.05). The association analysis of protein immunoexpression between the lesions studied revealed significant results for a high cytoplasmic expression of E-cadherin and LLSCCs (p = 0.001), high expression of α-SMA and LLSCCs (p < 0.001), low expression of TGF -β and LLSCCs (p < 0.001) and high expression of Snail and ACs (p = 0.006). Survival analysis revealed a high expression of α-SMA in tumor front stroma (p = 0.013), a network immunostaining pattern of this protein (p = 0.046) and high expression of TGF-β in tumor buds (p = 0.043) were significantly associated with worse OS, and LLSCCs with high expression of α-SMA also had a higher risk of death (HR = 5.90, p = 0.030). High cytoplasmic expression of TGF-β in tumor buds was significantly associated with both worse DFS (p = 0.007) and higher risks of negative outcomes for DFS (HR = 4.44; p = 0.014). The results of present study suggest that although the immunoexpression of evaluated proteins does not indicate differences in degree of histopathological severity in ACs, dysregulations of these proteins were identified among the lesions studied. Furthermore, it was found that LLSCC with more aggressive behavior was associated with low expression of membrane E-cadherin, high expression of α-SMA and its network pattern, and low expression of TGF-β in tumor buds. Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq A transição epitélio-mesenquimal (TEM) é um processo biológico que vem sendo amplamente estudado em carcinoma epidermoide oral (CEO), porém, ainda raramente avaliado na carcinogênese labial. O objetivo deste estudo foi de investigar a imunoexpressão das proteínas E-caderina, α-SMA, TGF-β e Snail em queilites actínicas (QA) diagnosticadas histopatologicamente como displasias epiteliais, e em carcinomas epidermoides de lábio inferior (CELI). A imunoexpressão de E-caderina, α-SMA, TGF-β e Snail foi analisada de forma semiquantitativa em 54 casos de QAs e em 49 CELIs. Visando a associação dos achados imunoistoquímicos com as variáveis clinicopatológicas e taxas de sobrevida global (SG) e livre de doença (SLD), os casos foram classificados nas categorias baixa expressão e alta expressão. Não foram observadas associações estatisticamente significativas com nenhuma das proteínas analisadas com o grau de severidade das displasias epiteliais em QAs (p > 0,05). A análise imunoistoquímica em CELIs revelou que uma baixa expressão membranar da E-caderina no front tumoral estava significativamente associada a CELIs com ≥5 buds (p = 0,005) e alto escore tanto para o modelo BD (p = 0,009), quando para o proposto por Dourado et al. (2020) (p = 0,038), entretanto, não foram observadas associações significativas entre a imunoexpressão desta proteína com parâmetros clínicos (p > 0,05). Constatou-se ainda associações significativas entre baixa expressão de α-SMA com CELIs em estágios clínicos TNM I/II (p = 0,05), baixa profundidade de invasão (p = 0,006), < 5 buds (p = 0,027) e escore de risco baixo/intermediário, ao passo que a alta expressão desta proteína foi associada com o desfecho óbito (p = 0,009). Também foram encontradas associações significativas entre o padrão de imunomarcação em rede/em fuso de α-SMA com CELIs em estágios TNM III/IV (p = 0,031), com alta profundidade de invasão (p = 0,002), ≥5 buds (p = 0,027), alto escore de risco BD (p = 0,001) e desfecho óbito (p = 0,015). Em relação à proteína TGF-β, percebeu-se associações estatisticamente significativas entre sua baixa expressão em buds tumorais com ausências de metástase linfonodal (p = 0,047) e de recidiva locorregional (p = 0,042), contudo, não foram observadas significâncias com nenhum dos parâmetros morfológicos (p > 0,05). A análise imunoistoquímica da proteína Snail não revelou nenhuma associação significativa com os parâmetros clinicopatológicos (p > 0,05). A análise de associação das imunoexpressões das proteínas entre as lesões estudadas revelou resultados significativos para uma alta expressão citoplasmática da E-caderina e CELIs (p = 0,001), alta expressão de α-SMA e CELIs (p < 0,001), baixa expressão de TGF-β e CELIs (p < 0,001) e alta expressão de Snail e QAs (p = 0,006). A análise de sobrevida revelou que uma alta expressão de α-SMA no estroma do front tumoral (p = 0,013), padrão de imunomarcação em rede desta proteína (p = 0,046) e alta expressão de TGF-β em buds tumorais (p = 0,043) estavam significativamente associadas à pior SG, além de que CELIs com alta expressão de α-SMA também apresentavam maior risco de óbito (HR = 5,90, p = 0,030). Uma alta expressão citoplasmática de TGF-β em buds tumorais estava significativamente associada tanto à pior SLD (p = 0,007), quanto a maiores riscos de desfechos negativos para a SLD (HR = 4,44; p = 0,014). Os resultados do presente estudo sugerem que apesar da imunoexpressão das proteínas avaliadas não indicarem diferenças no grau de severidade histopatológica em QAs, desregulações dessas proteínas foram identificadas entre as lesões estudadas. Ademais, foi constatado que CELI com comportamento mais agressivo estava associado a baixa expressão da E-caderina membranar, alta expressão de αSMA e seu padrão em rede e baixa expressão de TGF-β em buds tumorais. 2021-08-13T16:02:27Z 2021-08-13T16:02:27Z 2021-06-25 masterThesis MORAIS, Hannah Gil de Farias. Imunoexpressão das proteínas E-caderina, α-SMA, TGF-β e Snail em queilites actínicas e carcinoma epidermoide de lábio inferior. 2021. 125f. Dissertação (Mestrado em Ciências Odontológicas) - Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, 2021. https://repositorio.ufrn.br/handle/123456789/33126 pt_BR Acesso Aberto application/pdf Universidade Federal do Rio Grande do Norte Brasil UFRN PROGRAMA DE PÓS-GRADUAÇÃO EM CIÊNCIAS ODONTOLÓGICAS