RESUMEN
Canine mast cell tumour (MCT) is a biologically heterogeneous disease. The extracellular matrix degradation promoted by matrix metalloproteinases (MMPs) has been studied in an attempt to elucidate the mechanisms involved in the biological behaviour of tumours. The aim of this study was to characterize the expression of MMP-2 and -9 and tissue inhibitors of metalloproteinase (TIMP)-1 and -2 in canine cutaneous MCTs and to evaluate their prognostic values. Immunohistochemical staining for MMP-2, MMP-9, TIMP-2 and TIMP-1 was performed in 46 canine cases of MCTs. TIMP-1 expression showed an independent prognostic value for post-surgical survival and disease-related mortality. Dogs with MCTs showing less than 22.9% mast cell TIMP-1 positivity were more prone to die because of the disease and had a shorter post-surgical survival. This article suggests the involvement of TIMP-1 in MCT progression, by contributing to a good outcome in patients with MCTs.
Asunto(s)
Enfermedades de los Perros/enzimología , Mastocitoma Cutáneo/veterinaria , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Animales , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/mortalidad , Perros , Femenino , Masculino , Mastocitoma Cutáneo/diagnóstico , Mastocitoma Cutáneo/enzimología , Mastocitoma Cutáneo/mortalidad , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Pronóstico , Análisis de Supervivencia , Inhibidor Tisular de Metaloproteinasa-2/metabolismoRESUMEN
Minichromosome maintenance proteins (MCMs) are sensitive markers of cellular proliferation and have been shown to be significant predictors of survival in several human malignancies. MCM7 was evaluated as a prognostic marker in canine cutaneous mast cell tumours (MCTs). MCM7 immunohistochemistry was performed and an index of MCM7-positive cells calculated in dogs with known outcome. The Receiver Operating Characteristics method was used to individuate the best cut-off value of MCM7 score as predictor of survival. Survival analysis and prognostic variables were analysed with statistical methods. Ninety-five dogs were included with 31 dying of MCTs. A value of 0.18 was used as cut-off value of MCM7 score as a binary variable. The median survival time for MCM7 score ≤0.18 was not reached at 3668 days, whereas for MCM7 score >0.18 was 187 days (log-rank test; P < 0.0001). In the multivariable analysis, MCM7 was significantly associated with survival after controlling for age, surgical margins and histological grade (hazard ratio 9.2; P = 0.001).