Expressions of Matrix Metalloproteinases 2, 7, and 9 in Carcinogenesis of Pancreatic Ductal Adenocarcinoma.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease, usually diagnosed in an advanced stage which gives a slight chance of recovery. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that participate in tissue remodeling and stimulate neovascularization and inflammatory response. The aim of the study was to evaluate the expression of MMP-2, MMP-7, and MMP-9 in normal ducts, tumor pancreatic adenocarcinoma cells, and peritumoral stroma in correlation with clinicohistopathological parameters. The study material was obtained from 29 patients with pancreatic ductal adenocarcinoma. The expressions of MMP-2, MMP-7, and MMP-9 were performed by immunohistochemical technique. Microvessel density (MVD) was visualized by special immunostaining. The expressions of MMP-2, MMP-7, and MMP-9 were mainly observed in tumor cells and peritumoral stroma. MMP-2 expression in cancer cells was correlated with female gender, stronger inflammation, and histopathological type of cancer (R = 0.460, p = 0.013; R = 0.690, p = 0.0001; R = −0.440, p = 0.005, resp.). The expression of MMP-7 in tumor cells was found to positively correlate with the presence of necrosis and negatively correlate with MVD (R = 0.402, p = 0.031; R = −0.682, p = 0.000). We also showed that positive MMP-9 expression in tumor cells was associated with MVD (R = 0.368, p = 0.084); however, it was not statistically significant. Our results demonstrate that MMP-2, MMP-7, and MMP-9 expressions correlate with various morphological features of the PDAC tumor such as inflammation, necrosis, and formation of the new blood vessels.