Banca de DEFESA: LEORIK PEREIRA DA SILVA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : LEORIK PEREIRA DA SILVA
DATE: 22/11/2019
TIME: 14:30
LOCAL: AUDITÓRIO DO DEPARTAMENTO DE ODONTOLOGIA
TITLE:

ANALYSIS OF THE RELATIONSHIP BETWEEN THE EXPRESSION OF TUMOR CELL MARKERS (ALDH-1 and SOX-2) AND THE CLINICOPATHOLOGICAL FEATURES OF SALIVARY GLAND TUMORS

KEY WORDS:

Salivary glands; Neoplasms; Stem cells; Immunohistochemistry; Western blot.

PAGES: 160
BIG AREA: Ciências da Saúde
AREA: Odontologia
SUMMARY:

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 through western blot and immunohistochemistry the expression of SC-related markers (ALDH-1 and SOX-2) in salivary gland neoplasms and their possible association with clinicopathological data. 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). Clinicopathological data and patient outcomes were retrieved from medical records. Data were recorded in Microsoft Excel software and transferred to 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 with clinical stage II. Protein expression assessed by immunohistochemistry and 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 Disease-free survival at 5 and 10 years were lower in patients diagnosed with adenoid cystic carcinoma, T3-T4 tumors, presence of metastases, clinical stage III-IV, recurrence and stromal expression of ALDH-1. Multivariate analysis showed advanced clinical stage and stromal expression of ALDH-1 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 mesenchymal stem cells may be directly related to the biological behavior and progress of malignant tumors in the salivary gland.

BANKING MEMBERS:
Externa à Instituição - ANA PAULA VERAS SOBRAL - UPE
Externo à Instituição - CASSIANO FRANCISCO WEEGE NONAKA - UEPB
Presidente - 346077 - LELIA BATISTA DE SOUZA
Interno - 2859541 - PEDRO PAULO DE ANDRADE SANTOS
Interna - 350484 - ROSEANA DE ALMEIDA FREITAS