Avaliação da expressão de proteínas envolvidas na evasão tumoral no carcinoma mucoepidermóide de glândula salivar menor
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2017-02-21
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Universidade Federal de Goiás
Resumo
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.
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MOSCONI, Carla. Avaliação da expressão de proteínas envolvidas na evasão tumoral no carcinoma mucoepidermóide de glândula salivar menor. 2017. 36 f. Dissertação (Mestrado em Odontologia) - Universidade Federal de Goiás, Goiânia, 2017.