Avaliação da expressão de proteínas envolvidas na evasão tumoral no carcinoma mucoepidermóide de glândula salivar menor

• Ano de defesa: 2017
• Autor(a) principal: Mosconi, Carla
• Orientador(a): Batista, Aline Carvalho
• Banca de defesa: Aline Carvalho Batista, Aline Carvalho Batista, Vêncio, Eneida Franco, Alves, Pollianna Muniz
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Goiás
• Programa de Pós-Graduação: Programa de Pós-graduação em Odontologia (FO)
• Departamento: Faculdade de Odontologia - FO (RG)
• País: Brasil
• Palavras-chave em Português: Antígenos HLA; Proteína 1 ligante de morte celular programada 1; Carcinoma mucoepidermóide; Neoplasias das glândulas salivares; Evasão da resposta imune
• Palavras-chave em Inglês: HLA antigens; Programmed cell death 1 ligand 1 protein; Mucoepidermoid carcinoma; Salivary gland
• Área do conhecimento CNPq: ODONTOLOGIA::CLINICA ODONTOLOGICA
• Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tede/9775

Background: The Human Leukocyte Antigen G and E (HLA-G and HLA-E) and Programmed Death Ligand-1 (PD-L1) are molecules which can provide tumor immunosuppression as well as the capacity of neoplastic evasion or escape to the immune system host. Objective: To identify the expression of HLA-G, HLA-E and PD-L1 in oral mucoepidermoid carcinomas (MEC) and assess whether such expressions are related to metastasis, survival, staging, localization and tumor grade. Design: This cross-sectional study selected samples of MEC minor salivary glands (n=30) and classified them according to the World Health Organization (WHO) grading as low grade (LG), intermediate grade (IG) and high grade (HG). HLA-G, HLA-E and PD-L1 were identified by immunohistochemistry and measured by the proportion of positive neoplastic (mucous, epidermoid, intermediate and clear) and stromal cells. The density of positive Cytotoxic T Lymphocytes (CTLs), Natural Killer (NK), and Granzyme B (GB) cells was also evaluated. The Kruskal-Wallis test was used with a 5% significance level. Results: Expressions of HLA-G, HLA-E and PD-L1 were identified in the majority of epidermoid, intermediate and clear cells, but not in the mucous cells of the MECs. Thus, the quantitative analysis of the total percentage of positive neoplastic cells showed an association between the expression of these proteins and histologic grading with the following median values: HLA-G (LG= 79%, IG= 96%, HG= 99%; p=0.0004), HLA-E (LG= 70%, IG= 96%, HG= 99%; p<0.0001) and PD-L1 (LG= 34%, IG= 79%, HG= 80%; p=0.01). In consonance with a microenvironment conducive to inhibiting CTLs and NK cells, low GB density was found in all MEC samples. There was no relationship between the percentage of HLA-G+, HLA-E+ and PD-L1+ cancer cells and the other clinical parameters evaluated. Conclusions: MEC expresses a set of proteins involved in neoplastic cell escape from the anti-tumor immune system. In addition, increased expression of HLA-G, HLA-E and of PD-L1 in the tumoral microenvironment is closely related to the predominant cell type, and consequently to the higher histologic grades of MEC.