Immunohistochemical study of proteins of plasminogen activator system in benign epithelial odontogenic lesions
Urokinase-type plasminogen activator. Odontogenic tumors. Odontogenic cysts. Immunohistochemistry.
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 possible correlations between the immunoexpression of PAS proteins (uPA, uPAR and PAI-1) in ameloblastomas (AMBs) and odontogenic keratocysts (OKs), comparing with dental follicles (DFs). 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 cystic growth of OKs, while uPAR participates in tumorigenesis process of AMBs. Despite the important biological functions performed by PAI-1, this protein may not directly contribute to the pathogenesis of AMBs and OKs.