Serous and mucinous ovarian tumors express different profiles of MMP-2, -7, -9, MT1-MMP, and TIMP-1 and -2

Abstract

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play key roles in tumorigenesis, but little is known of their expression according to mucinous or serous type. This study aimed to evaluate the immunohistochemical expression of MMP-2, -7, -9, MT1-MMP, TIMP-1 and -2 in these tumors. A tissue microarray was set up including 99 serous (25 benign, 27 borderline, 47 malignant) and 79 mucinous (25 benign, 44 borderline, 10 malignant) ovarian tumors. Immunostaining results were scored by using the HSCORE and assessed by univariate, unsupervised hierarchical clustering and multidimensional scaling analyses. Epithelial expression of MMP-2, -7, -9, MT1-MMP, TIMP-2, but not TIMP-1, was higher in serous than mucinous tumors. Stromal expression of MMP-7 was higher in serous tumors. Alterations in MT1-MMP, MMP-7 and -9 were found in malignant serous tumors, while benign and borderline tumors shared similar expressions. By unsupervised hierarchical clustering analysis, mucinous and serous tumors were better differentiated by epithelial than stromal MMP and TIMP immunolabelling. By multidimensional scaling analysis, the expressions of MMPs and TIMPs were scattered in serous tumors and homogeneous for mucinous tumors. In conclusion, our results support the differential expression in MMPs and TIMPs of ovarian tumors according to serous or mucinous histology.