Expression of mmp-2, mmp-9 and uPAR in normal canine prostates c proliferative lesions / Expressão de mmp-2, mmp-9 e upar em próstatas caninas normais e c lesões proliferativas

Mariana Batista Rodrigues Faleiro

Humans and dogs show dysplastic lesions in the prostate, such as prostatic intraepithelial neoplasms (PIN) and proliferative inflammatory atrophy (PIA), which are studied due to their malignance potential. The matrix metalloproteinases (MMP) are a family of proteolytic enzymes thought to play an important role in tumor invasion and metastasis in face of their ability to degrade the extracellular matrix (ECM) and basement membrane. The plasminogen activator (PA) system has been suggested to play a central role in cell adhesion, migration, wound healing, angiogenesis, inflammation, regulation of growth factors and tumor invasion. The receptor of plasminogen activator type activator (uPAR) is a component of the PA, with a range of expression in tumor cell and stromal cells. So, this study was aimed to evaluated the expression and correlation between MMP-2 (gelatinase A) and MMP-9 (gelatinase B) as well as the expression of uPAR in normal canine prostate tissue and also in tissue with proliferative disorders, including benign prostatic hyperplasia (HPB), PIA, PIN and carcinoma. And therefore establish relation among the role of these enzymes in the remodeling of the extracellular matrix (ECM) and in the process of tumor invasion and metastasis. For this, it was performed immunohistochemical staining in tissue microarray of 149 paraffin-embedded fragments of prostate tissue selected from 57 prostates of non-castrated adult dogs with or without prostatic diseases. A total of 298 cores were analyzed and it was made 363 diagnoses: 36 (9.9%) normal, 49 (13.5%) BPH, 132 (36.3%) PIA, 75 (20.7%) PIN and 71 (19.6%) carcinomas. It was observed differences in cytoplasmatic immunohistochemical staining by MMP-2 and MMP-9 antibodies in relation to the cell number and intensity of labeling of the acinar epithelial and stromal perilobular cells between normal tissue and in those with proliferative disorders. A correlation between MMP-2 and MMP-9 antibodies occurred just in canine prostates with PIA in relation to the number of labeled cells in acinar epithelium and perilobular stroma, as well as, the staining intensity in the perilobular stromal cells. In relation to uPAR, it was observed differences of immunohistochemical staining of uPAR antibodies in canine prostate. Likewise, there was over expression in dysplastic and neoplasic specimens, but not in normal and benign prostate tissue. A number of epithelial cells labeled for uPAR showed variation among the diagnoses, except between PIN and carcinoma. Less intensity of labeling was observed in acinar epithelial cells of normal prostates compared with PIA, PIN and carcinoma. However, in the normal cells and in those with PIA, there was a difference in the number of cells, as well as in the intensity of stromal labeling. The intensity of labeling of stromal perilobular cells was higher in the PIA. PIA-A (accentuated) and PIA-M (moderated) cells showed greater intensity staining stroma and stromal cells labeled for uPAR, respectively. Thus, this study concludes that there was variation in gelatinases and uPAR expression in canine prostate according to the lesion. Also, there was Less labeling in normal and BPH and higher in PIA, PIN and carcinoma prostate tissues. The correlation between MMP-2 and MMP-9 in canine prostates with PIA indicates that the inflammation likely influenced the activity of these enzymes with simultaneous increase in their expression. The uPAR high expression in inflammatory and neoplasic tissues suggests high ECM proteolytic activity in these situations

Expression of mmp-2, mmp-9 and uPAR in normal canine prostates c proliferative lesions / Expressão de mmp-2, mmp-9 e upar em próstatas caninas normais e c lesões proliferativas

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