title: Immunohistochemical evaluation of MMP-2 and TIMP-2 in canine mammary tumours: a survival study.
abstract: Canine mammary tumours (CMTs) are a very heterogeneous group of neoplasms with variable prognosis. Their aggressiveness is mainly due to their ability to invade locally and to metastasize. The degradation of extracellular matrix components is an important determinant of the invasive phenotype. The aims of this study were to analyse by immunohistochemistry and double immunofluorescence the expression of metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) in eight normal canine mammary glands and 118 CMTs (24 benign, 94 malignant) and to investigate relationships with metastatic disease and survival. MMP-2 and TIMP-2 expression was higher in malignant tumours than in normal canine mammary tissue and benign tumours. The main difference between benign and malignant CMTs was the pattern of expression of both molecules: benign tumours presented TIMP-2 and MMP-2 immunoreactivity in the myoepithelial cells lining the basement membrane of tubuloalveolar structures, while malignant tumours showed mainly diffuse expression in neoplastic cells. In malignant tumours, increased TIMP-2 expression was significantly associated with the development of distant metastases, lower overall survival and lower disease-free survival. MMP-2 expression was not significantly associated to any of these parameters. These results suggest that the immunohistochemical expression of TIMP-2 is a useful prognostic factor in CMTs.
authors.affiliation: Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Largo Professor Abel Salazar, 2, 4099-003 Porto, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Santos
authors.forename: Célia
authors.initials: C
authors.lastname: Lopes
authors.forename: Carlos
authors.initials: C
authors.lastname: Frias
authors.forename: Irina
authors.initials: I
authors.lastname: Amorim
authors.forename: Corália
authors.initials: C
authors.lastname: Vicente
authors.forename: Fátima
authors.initials: F
authors.lastname: Gärtner
authors.forename: Augusto de
authors.initials: Ad
authors.lastname: Matos
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D004283:Dog Diseases / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004285:Dogs; D005260:Female; D005500:Follow-Up Studies; D007150:Immunohistochemistry / Q000662:veterinary; D015674:Mammary Neoplasms, Animal / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016019:Survival Analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2