Matrix Metalloproteinase Expression in Canine Cutaneous Mast Cell Tumours: Clinicopathological Associations and Prognostic Value of MMP-9

Canine cutaneous mast cell tumours (MCTs) exhibit variable biological behaviour, requiring additional prognostic biomarkers to refine risk stratification. This study evaluated matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9 immunohistochemical expression in 90 paraffin-embedded cutaneous MCTs, assessing correlations with clinicopathological features and outcome. MMP-9 expression significantly associated with histological grade (p = 0.001), tumour size (p = 0.040), age (p = 0.021), Ki-67 index (p = 0.001), and c-KIT pattern (p = 0.040). Tumours with >50% MMP-9-positive neoplastic cells were all grade III (n = 6), showing strong associations with recurrence/metastasis (p = 0.016) and tumour-related death (p < 0.0001). Although histological grade remained the primary prognostic variable in multivariate decision-tree analysis, MMP-9 offered critical complementary stratification within grade I–II tumours; dogs with 25–50% MMP-9 positivity demonstrated lower survival than those with <25% positivity. MMP-1 expression correlated with histological grade, Ki-67 index, and c-KIT pattern, whereas MMP-2 showed no significant associations with grade or outcome. Overall, MMP-9 was identified as the metalloproteinase most consistently linked to aggressive tumour behaviour, supporting further investigation as a candidate prognostic marker. Its independent prognostic value and clinical utility remain to be established.