Immunolocalization of matrix metallo-proteinases and their tissue inhibitor in human mammary pathology

• Published in: Bulletin du cancer Vol. 79; no. 3; p. 261
• Main Authors: Clavel, C, Polette, M, Doco, M, Binninger, I, Birembaut, P
• Format: Journal Article
• Language: English
• Published: France 1992
• Subjects: Adult; Aged; Breast Neoplasms - enzymology; Collagenases - metabolism; Collagenases - physiology; Extracellular Matrix - enzymology; Female; Humans; Immunohistochemistry; Matrix Metalloproteinase 3; Metalloendopeptidases - metabolism; Metalloendopeptidases - physiology; Middle Aged
• ISSN: 0007-4551

Matrix metallo-proteinases (MMPs) are a group of enzymes thought to be responsible for both normal connective tissue matrix remodelling and accelerated breakdown associated with tumor development. The distribution of 3 major matrix metallo-proteinases was studied in human mammary pathology: collagenase (MMP1) which degrades fibrillar interstitial collagens, a 72-kDa gelatinase (MMP2) which mainly degrades type IV collagen and denatured collagens, and stromelysin (MMP3) which has a wider range of action, degrading several matrix components including the core proteins of proteoglycans, laminin and non-helical regions of collagens. These MMPs and the MMP tissual inhibitor (TIMP1) were detected by immunohistochemistry in 30 benign and 79 malignant lesions of the breast. MMPs were detected in 1 fibroadenoma (collagenase) and 22 breast carcinomas: collagenase (9 cases), stromelysin (12 cases) and gelatinase (16 cases) with a limited distribution. Tumor cells were preferentially labelled and the localization of gelatinase and stromelysin at the periphery of some non-invasive and well-differentiated clusters supports the role of these enzymes in the breakdown of basement membranes. Only a few stromal cells (fibroblasts) were found to be immunopositive. In contrast, TIMP1 was more frequently detected, and was found in 7 benign lesions and 55 carcinomas out of 79. It was mainly localized at the periphery of the endothelial cells but was occasionally detected in cancer cells and fibroblasts.