Preliminary Observations on Matrix Metalloproteinases in Canine Oral Melanoma: Association Of MMP-9 and TIMP-2 Immunohistochemical Expression with FXR1 and Clinical Outcome,

Introduction: Feline diffuse iris melanoma (FDIM) is the most common feline primary intraocular neoplasm. It is a slowly progressive malignant tumour, representing a possiblemodel of human iris melanoma. In cats, histological grade andmitotic index (MI) are considered predictors of survival. Matrix metalloproteinase-9 (MMP-9) is an endopeptidase able to digest the extracellular matrix and is involved in tumour invasion. Its specific inhibitor is the tissue inhibitor of metalloproteinases-2 (TIMP-2). The present study investigates the correlation between MMP-9/TIMP-2 expression and histological grade and MI. Materials and Methods: Sixty-one FDIMs were graded on light microscopy (grade I, n 5 22; grade II, n 5 20; grade III, n 5 19) and MI was calculated. Immunohistochemistry was performed using monoclonal anti-MMP-9 and anti-TIMP-2 antibodies and scored semiquantitatively. Results were compared by the Mann-Whitney U test. Results: MMP-9 was expressed in 59.1% grade I FDIMs, 90.0% grade II and 80.0% grade III tumours.TIMP-2 immunolabelled 59.1% grade I, 80.0% grade II and 73.7% grade IIIFDIMs.MMP-9was expressed in 71.4% of FDIMswithMI7 and 92.3% of FDIMwithMIO7. TIMP-2 was detected in 67.3% of caseswithMI7 and 76.9% of caseswithMI O7. MMP-9 and TIMP-2 expression differed significantly between grade I and the other two grades. TIMP-2 expression was correlated withMMP-9 expression in grade I and III tumours. IntenseMMP-9, but not TIMP-2, was significantly associated with high MI. Conclusions: In FDIM intense immunohistochemical expression of MMP-9 correlated with known histological parameters of aggressiveness, specifically histological grade and MI.