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Doctoral Thesis
DOI
https://doi.org/10.11606/T.25.2021.tde-06122021-120350
Document
Author
Full name
Silas Antonio Juvencio de Freitas Filho
Institute/School/College
Knowledge Area
Date of Defense
Published
Bauru, 2020
Supervisor
Committee
Oliveira, Denise Tostes (President)
Camillo, Cláudia Malheiros Coutinho
Cardoso, Sérgio Vitorino
Santos, Paulo Sergio da Silva
Title in Portuguese
Imunoexpressão de marcadores de células-tronco tumorais em subtipos de carcinomas espinocelulares de boca
Keywords in Portuguese
ALDH1
Câncer de boca
Notch1
Abstract in Portuguese
O objetivo do presente estudo foi investigar o significado clínico e o valor prognóstico da imunoexpressão dos marcadores de células-tronco tumorais, ALDH1 e Notch1 em câncer de boca. Foram avaliados por meio da técnica de imuno-histoquímica a expressão de ALDH1 e Notch1 em 63 pacientes com carcinomas espinocelulares de boca e seus subtipos, o carcinoma verrucoso e o carcinoma escamoso basalóide. A análise semi-quantitativa da imunoexpressão de ALDH1 e Notch1 no front de invasão tumoral foi realizada e associada com as variáveis clinicopatológicas pelo teste qui-quadrado ou teste exato de Fisher. As probabilidades de sobrevivência global e livre de doença, em cinco anos, foram estimadas pelo método de Kaplan-Meier sendo as curvas comparadas pelo teste log-rank. O modelo de regressão de Cox foi aplicado para verificar a influência das variáveis clinicopatológicas significativas no prognóstico. O nível de significância de 5% foi considerado em todos os testes estatísticos. Os resultados mostraram que a forte expressão para ALDH1 foi observada em 16 carcinomas espinocelulares de boca (25,4%) e para Notch1 em 27 carcinomas espinocelulares de boca (42,9%). A maioria dos tumores com forte imunoexpressão de ALDH1 foi carcinoma escamoso basalóide (56,3%). Associações estatisticamente significativas foram observadas entre a forte imunoexpressão de Notch1 em carcinomas espinocelulares pouco diferenciados com infiltração perineural (p=0,011) e comprometimento linfonodal histopatológico (pN+) (p=0,034). A imunoexpressão de Notch1 não foi fator de prognóstico significativo, entretanto a forte imunoexpressão de ALDH1 foi fator de prognóstico associado com pior sobrevivência global (p=0,040) para os pacientes com câncer de boca. Conclui-se que a forte imunoexpressão de Notch1 pode contribuir com a identificação de pacientes com carcinomas espinocelulares pouco diferenciados de boca que apresentam infiltração perineural e metástases linfonodais. Além disso, a forte imunoexpressão de ALDH1 pode ajudar a identificar um pior prognóstico nos pacientes com carcinomas espinocelulares de boca e seus subtipos.
Title in English
Immunoexpression of cancer stem cell markers in subtypes of oral squamous cell carcinomas
Keywords in English
ALDH1
Notch1
Oral cancer
Abstract in English
The present study aimed to investigate the clinical significance and prognostic value of the immunoexpression of cancer stem cell markers, ALDH1 and Notch1, in oral cancer. The expression of ALDH1 and Notch1 in 63 patients with oral squamous cell carcinomas and their subtypes, verrucous carcinoma and basaloid squamous cell carcinoma were evaluated by immunohistochemistry. The semi-quantitative analysis of the immunoexpression of ALDH1 and Notch1 at the invasive tumor front was performed and associated with clinicopathological variables using the chi-square test or Fisher's exact test. The probabilities of global and disease-free survival in five years were estimated using the Kaplan-Meier method and the curves were compared using the log-rank test. The Cox's regression model was applied to verify the influence of significant clinicopathological variables on the prognosis. The significance level of 5% was considered in all statistical tests. The results showed that the strong expression for ALDH1 was observed in 16 oral squamous cell carcinomas (25.4%) and for Notch1 in 27 oral squamous cell carcinomas (42.9%). Most tumors with strong immunoexpression of ALDH1 were basaloid squamous cell carcinoma (56.3%). Statistically significant associations were observed between the strong immunoexpression of Notch1 in poorly differentiated oral squamous cell carcinomas with perineural infiltration (p=0.011) and lymph node involvement (pN+) (p=0.034). The immunoexpression of Notch1 was not a significant prognostic factor, however, the strong immunoexpression of ALDH1 was a prognostic factor associated with worse overall survival (p=0.040) for patients with oral cancer. In conclusion, the strong immunoexpression of Notch1 can contribute to the identification of patients with poorly differentiated oral squamous cell carcinomas who have perineural infiltration and lymph node metastasis. Moreover, the strong immunoexpression of ALDH1 may help to identify an unfavorable prognosis in patients with oral squamous cell carcinomas and their subtypes.
 
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Publishing Date
2021-12-06
 
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