Matrix metalloproteinase expression in human breast cancer: an immunohistochemical study including correlation with cathepsin D, type IV collagen, laminin, fibronectin, EGFR, c-erbB-2 oncoprotein, p53, steroid receptors status and proliferative indices.
Matrix metalloproteinases (MMPs) are a group of enzymes thought to be responsible for both normal connective tissue matrix remodelling and accelerated breakdown associated with tumour development. The current study aimed to investigate the immunohistochemical expression of matrix metalloproteinase 3 (MMP-3, stromelysin-1) in correlation with the expression of Basement Membrane (BM) antigen (type IV collagen, laminin), fibronectin, cathepsin D, p53, c-erbB-2, proliferative activity (Ki-67, PCNA), steroid receptor content as well as to the other conventional clinicopathological parameters in breast cancer. This study was performed on a series of frozen and paraffin sections from 84 breast cancer specimens by immunohistochemistry using the monoclonal antibody MMP-3 (Ab-1). Stromelysin-1 (ST1) was observed in about 10% of epithelial cells in the control groups (cases of fibrocystic and benign proliferative breast disease), while expression (> 10% of expression) was detected in 89.7% of tumours. The expression of ST1 in carcinoma cells was strongly associated with its presence in the stroma (p < 0.001). A significantly positive correlation was found between ST1 expression, and p53 tumour suppressor gene product (p = 0.004), and a relationship with c-erbB-2 protein and progesterone receptor status was also indicated. These findings suggest that ST1 expression in breast cancer tissue is irrespective of the expression of the extracellular matrix component, the proteolytic enzyme cathepsin D and the growth fraction of the tumour, and that it could be a potential new prognostic marker in breast cancer.
Ioachim
E E
EE
Department of Pathology, University Medical School of Ioannina, Greece.
Athanassiadou
S E
SE
Kamina
S
S
Carassavoglou
K
K
Agnantis
N J
NJ
D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology; D002402:Cathepsin D / Q000032:analysis; D003094:Collagen / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D005353:Fibronectins / Q000032:analysis; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D007797:Laminin / Q000032:analysis; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D019278:Matrix Metalloproteinase 3 / Q000032:analysis / Q000096:biosynthesis*; D008940:Mitotic Index; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D002402:Cathepsin D; D003094:Collagen; D066246:ErbB Receptors; D005353:Fibronectins; D019394:Ki-67 Antigen; D007797:Laminin; D019278:Matrix Metalloproteinase 3; D018809:Proliferating Cell Nuclear Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53