title: Matrix metalloproteinase-9 expression in mammary gland tumors in dogs and its relationship with prognostic factors and patient outcome.
abstract: OBJECTIVE
  To immunohistochemically evaluate matrix metalloproteinase (MMP)-9 expression in benign and malignant mammary gland tumors (MMTs) in dogs and relate expression to prognostic factors and patient outcome.
  
  
  METHODS
  118 female dogs with naturally occurring mammary gland tumors and 8 dogs without mammary gland tumors.
  
  
  METHODS
  24 benign mammary gland tumors and 94 MMTs (1/affected dog) were obtained during surgical treatment; control mammary gland tissue samples were collected from unaffected dogs after euthanasia for reasons unrelated to the study. Tumors were evaluated for proliferation, invasive growth, histologic grade, and metastatic capacity; expression of MMP-9 was determined immunohistochemically, and its relationship with clinical and histologic findings was investigated. For dogs with MMTs, follow-up continued for 2 years; data were used to compute overall survival time and disease-free interval and construct survival curves.
  
  
  RESULTS
  MMTs had significantly higher MMP-9 expression in stromal cells and in neo-plastic cells than did the benign neoplasms. Stromal MMP-9 expression was also higher in highly proliferative tumors and in tumors with invasive growth, high histologic grade, and metastatic capacity. Furthermore, tumors from patients with shorter overall survival times and disease-free intervals had higher expression of MMP-9 in stromal cells.
  
  
  CONCLUSIONS
  In dogs with MMTs, level of MMP-9 expression by stromal cells was related to factors of poor prognosis and shorter overall survival times and disease-free intervals. These results suggested that MMP-9 produced by tumor-adjacent stromal cells contributed to MMT progression in female dogs and that assessment of MMP-9 expression may be a valuable prognostic factor.
authors.affiliation: Department of Veterinary Clinics, University of Porto, Porto, Portugal.
authors.forename: Andreia A
authors.initials: AA
authors.lastname: Santos
authors.forename: Célia C
authors.initials: CC
authors.lastname: Lopes
authors.forename: Raquel M
authors.initials: RM
authors.lastname: Marques
authors.forename: Irina F
authors.initials: IF
authors.lastname: Amorim
authors.forename: Maria F
authors.initials: MF
authors.lastname: Gärtner
authors.forename: Augusto J F
authors.initials: AJ
authors.lastname: de Matos
mesh_terms: D000818:Animals; D016009:Chi-Square Distribution; D018450:Disease Progression; D004283:Dog Diseases / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D004285:Dogs; D005260:Female; D005500:Follow-Up Studies; D007150:Immunohistochemistry / Q000662:veterinary; D008321:Mammary Glands, Animal / Q000166:cytology / Q000473:pathology; D015674:Mammary Neoplasms, Animal / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D011379:Prognosis; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D044767:Ubiquitin-Protein Ligases; D014568:Urokinase-Type Plasminogen Activator; D020780:Matrix Metalloproteinase 9