Estudo da imunoexpressão de proteínas do sistema ativador de plasminogênio em lesões benignas do epitélio odontogênico

Abstract

Background: Odontogenic cysts and tumors are lesions originated from odontogenic tissues and exhibit different biological behaviors. Among the various elements that may be associated with cystic and tumor growth are the enzymes required for extracellular matrix (ECM) degradation. The plasminogen activator system (PAS) is responsible for regulating ECM remodeling by converting plasminogen to plasmin. In addition, several studies have suggested associations between PAS and other factors in the evolution of malignant neoplasms, such as epithelial-mesenchymal transition, proliferation, migration, cell adhesion, and metastatic dissemination. However, just a few studies have evaluated the influence of PAS on odontogenic lesions. Aim: To evaluate and to compare the immunohistochemical expression of PAS proteins, the urokinase-type plasminogen activator (uPA), its receptor (uPAR) and inhibitor (PAI-1) in ameloblastomas (AMBs), odontogenic keratocysts (OKCs) and normal odontogenic tissues, dental follicles (FDs), in addition to investigating possible correlations between these proteins. Materials and methods: Odontogenic epithelial cells were analyzed, in a semi-quantitative way, using photomicrographs of 5 representative fields of each case, with 400x magnification, with scores ranging from 0 to 4 according to the percentage of positive cells. After the analysis of 5 fields, the median of the scores was obtained, generating the immunostaining score of the case. The data were submitted to statistical analysis using Kruskal-Wallis (KW) and Mann-Whitney (U) tests and Spearman’s correlation (r), with significance level set at 5% (p<0.05). Results: For uPA, the immunoexpression was significantly lower in AMBs, when compared to OKs (p=0.001) and DFs (p=0.029). While, uPAR immunostaining in AMBs was significantly higher compared to OKs (p<0.001). There were no significant differences in PAI-1 immunoexpression between the groups studied (p=0.775). There were also no statistically significant correlations between the evaluated proteins (p>0.05). Conclusions: The results of this study suggest that uPA is involved in growth of OKCs, while uPAR participates in tumorigenesis process of AMBs, however, PAI1 does not seem to contribute, directly, to the pathogenesis of AMBs and OKCs. In the context of the studied lesions, SAP proteins do not seem to act synergistically.