title: The multifunctional role of the immunohistochemical expression of MMP-7 in invasive breast cancer.
abstract: The secretion of matrix metalloproteinases (MMPs) is crucial in the metastasis of cancer cells, since MMPs are responsible for the degradation of extracellular matrix (ECM). Among them, matrix metalloproteinase-7 (MMP-7) or matrilysin 1 is a stromelysin which degrades type-IV collagen, fibronectin and laminin. Immunohistochemistry was performed to detect MMP-7 protein in infiltrative breast carcinomas. MMP-7 was studied along with clinicopathological parameters, disease-free and overall survival, and p53, c-erbB-2, topoIIa, MMP-2, uPAR and beta-catenin. MMP-7 immunoreactivity was detected in the cytoplasm of cancer cells in 54.2% (96/177) and tumor stromal cells in 47.5% (84/177), as well as in normal epithelium adjacent to malignant epithelium. MMP-7 reactivity in cancer cells displayed an inverse association with nuclear grade (p=0.049) and topoIIa (p=0.03). A parallel association was observed between the expression of MMP-7 in both malignant and stromal cells with uPAR in cancer cells (p=0.033 and p=0.027, respectively). MMP-7 of tumor stromal cells depicted a parallel correlation with MMP-2 of the same cell type (p=0.044), while abnormal beta-catenin expression was inversely associated with MMP-7 of cancer cells (p=0.047). Our results show the multifunctional role of MMP-7 in the mammary gland, since it seems to be associated with a less aggressive phenotype, while, at the same time, being involved in invasion, through its collaboration with indicators of invasion.
authors.affiliation: Department of Pathology, Medical School of Athens University, Alexandra Hospital, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Mylona
authors.forename: A
authors.initials: A
authors.lastname: Kapranou
authors.forename: J
authors.initials: J
authors.lastname: Mavrommatis
authors.forename: S
authors.initials: S
authors.lastname: Markaki
authors.forename: A
authors.initials: A
authors.lastname: Keramopoulos
authors.forename: L
authors.initials: L
authors.lastname: Nakopoulou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005260:Female; D018734:Genes, erbB-2 / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D037241:Mannose-Binding Lectins / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011956:Receptors, Cell Surface / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051176:beta Catenin
chemical_list: D015415:Biomarkers; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; C404106:MRC2 protein, human; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2