Análise da relação entre a expressão de marcadores de células tronco tumorais (ALDH-1 e SOX-2) e as características clinico patológicas de neoplasias de glândulas salivares
The molecular and cellular mechanisms that are associated with pathogenesis, poor treatment response, recurrence, and death in salivary gland tumors are not fully known. In this matter, stem cells (SC) within a tumor (TSC) are related to tumorigenicity and progress in human neoplasms. As such, th...
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| Formato: | doctoralThesis |
| Idioma: | pt_BR |
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| Endereço do item: | https://repositorio.ufrn.br/jspui/handle/123456789/28382 |
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| Resumo: | The molecular and cellular mechanisms that are associated with pathogenesis, poor
treatment response, recurrence, and death in salivary gland tumors are not fully known.
In this matter, stem cells (SC) within a tumor (TSC) are related to tumorigenicity and
progress in human neoplasms. As such, the aim of this study was to evaluate the
expression of SC-related markers (ALDH-1 and SOX-2) in salivary gland neoplasms and
their possible association with clinicopathological data and patient outcomes. We selected
103 cases of malignant neoplasms (25 mucoepidermoid carcinoma; 15 acinic cell
carcinoma; 13 adenoid cystic carcinoma; 10 polymorphous adenocarcinoma; 13
adenocarcinoma NOS; 8 epithelial-myoepithelial carcinoma; 7 carcinoma ex
pleomorphic adenoma; 5 salivary duct carcinoma; 4 basal cell adenocarcinoma; 3 clear
cell carcinoma) and 51 cases of benign neoplasms (25 pleomorphic adenoma; 9
myoepithelioma; 7 Warthin tumor; 5 canalicular adenoma; 5 basal cell adenoma). Data
were analyzed in Statistical Package for Social Science, GraphPad Prism and STATA
softwares. A significance level of 5% was adopted for the statistical tests (p<0.05). Most
patients were male, with a mean age of 52 years, and the parotid was the most common
anatomical site. Most malignant neoplasms were classified as T1-T2, N0 and M0. Protein
expression assessed by immunohistochemistry and confirmed by western blot showed
similar results that were statistically correlated for both SOX-2 (p<0.001) and ALDH-1
(p=0.039). Regarding the expression of SOX-2, most benign tumors were negative (n=39;
76.5%), and expression was only observed in tumors without myoepithelial
differentiation (p<0.0001). In the other hand, most of the malignant tumors were positive
for SOX-2 (n=54; 52.4%), being statistically significant (p=0.002). The expression
occurred in cases without myoepithelial differentiation (p=0.006) mainly in
mucoepidermoid carcinoma and clear cell carcinoma. No association was found between
SOX-2 expression and clinical parameters. ALDH-1 was frequently expressed in the
parenchyma of malignant (n=88; 85.6%) and benign (100%) neoplasms. Overall, the
presence of ALDH-1 in the parenchyma was not associated with clinical data of malignant
neoplasms; nevertheless, the cases of mucoepidermoid carcinoma with high expression
in the parenchyma were associated with advanced clinical stage (p=0.047). The
expression of ALDH-1 in tumor stroma cells occurred mainly in malignant neoplasms
(n=67; 65.0%), being associated with lymph node metastasis (p=0.032), advanced clinical
stage (p=0.008), recurrence (p=0.006) and death (p=0.013). Overall survival and Diseasefree survival at 5 and 10 years were lower in patients diagnosed with adenoid cystic
carcinoma, advanced clinical stage, recurrence and stromal expression of ALDH-1.
Multivariate analysis showed advanced clinical stage and stromal expression of ALDH1 were independent prognostic factors for disease-free survival. Based on the results, the
profile of TSC presents variations in different salivary gland tumors. The differential
expression of SOX-2 and ALDH-1 in these neoplasms suggests that there are different
subtypes of TSC that can be activated by distinct molecular pathways. Also, the presence
of ALDH-1 stromal expression characterizes cells with mesenchymal CT profile that may
be directly related to the biological behavior and progress of malignant tumors in the
salivary gland. |
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