Biomarcadores da transição epitélio-mesenquimal em desordens potencialmente malignas e carcinoma de células escamosas de língua oral
During oral carcinogenesis, malignant cells acquire an aggressive phenotype that results in increased individual motility and the ability to invade surrounding tissues. Therefore, malignant epithelial cells develop a regulatory and programmed process called epithelial-mesenchymal transition (EMT)...
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| Formato: | doctoralThesis |
| Idioma: | pt_BR |
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Universidade Federal do Rio Grande do Norte
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| Endereço do item: | https://repositorio.ufrn.br/handle/123456789/47053 |
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| Resumo: | During oral carcinogenesis, malignant cells acquire an aggressive phenotype that
results in increased individual motility and the ability to invade surrounding tissues.
Therefore, malignant epithelial cells develop a regulatory and programmed
process called epithelial-mesenchymal transition (EMT), which is crucial for the
acquisition of this aggressive malignant phenotype. The aim of the present study
was to investigate the role of immunohistochemical expression of EMT signaling
proteins in oral epithelial dysplasias and oral squamous cell carcinomas of the
tongue (OTSCC), evaluating their respective associations with clinicopathological
and prognostic parameters. Initially, aiming to obtain a deeper understanding of
the proposed topic, two systematic literature reviews were developed evaluating
the role of EMT as a possible prognostic marker in cases diagnosed as oral
epithelial dysplasia and the role of nuclear transcription factors associated with the
MET process in regulation of cellular plasticity and biological behavior in head and
neck squamous cell carcinoma cell lines. For the immunohistochemical study, 47
cases of oral epithelial dysplasias and 41 cases diagnosed with OTSCC were
selected, in which the immunoexpression of Twist1, Snail1, E-cadherin and Ncadherin proteins were analyzed. Possible associations between the expression
pattern of these proteins and the histopathological grading of epithelial dysplasias
and with the clinicopathological aspects, recurrence and survival in OTSCC were
investigated. Different staining patterns were observed between the analyzed
groups, with a significant loss of membrane E-cadherin expression in cases of
OTSCC compared to cases of oral epithelial dysplasias (p = <0.0001). Worse
overall survival was observed in cases with low membrane E-cadherin expression
(HR = 0.27; p = 0.033) and high cytoplasmic Twist1 expression (HR = 3.19; p =
0.010). When analyzing the expression intensity parameter alone, an association
was observed between high cytoplasmic N-cadherin intensity and overall survival
(HR = 4.93; p = 0.006). Our findings suggest that loss of E-cadherin expression
and increased expression of N-cadherin and nuclear transcription factors Twist1
and Snail1 are associated with the development and progression of oral
carcinogenesis. Alone, loss of membrane expression of E-cadherin and increased
cytoplasmic expression of Twist1 and N-cadherin were associated with worse survival. |
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