Original Article DOI: 10.1111/vco.12280 High COX-2 expression in canine mast cell tumours is associated with proliferation, angiogenesis and decreased overall survival H. Gregório 1,2 , T. Raposo 3 , F. L. Queiroga 2,4,5 , I. Pires 2,6 , L. Pena 7 and J. Prada 2,6 1 CHV, Centro Hospitalar Veterinário, Porto, Portugal 2 Department of Veterinary Sciences, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal 3 Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK 4 Center for Technology of Agro-Environment and Biological Sciences (CITAB), University of Trás-os-Montes and Alto Douro, Vila Real, Portugal 5 Center for the Study of Animal Sciences, CECA-ICETA, University of Porto, Porto, Portugal 6 CECAV, University of Trás-os-Montes and Alto Douro, Vila Real, Portugal 7 Department of Veterinary Medicine and Science, University Complutense of Madrid, Veterinary School Hospital, Madrid, Spain Abstract COX-2 overexpression is associated with several hallmarks of carcinogenesis such as proliferation, angiogenesis, invasion and metastasis. Fifty cases of canine mast cell tumours (MCT) were retrospectively evaluated and submitted to immunohistochemistry for COX-2, CD31, Ki-67, MAC-387 and CD3. Furthermore its relationship with clinicopathological variables and overall survival (OS) was analysed. COX-2 intensity (P = 0.016), but not COX-2 extension nor score was associated with decreased OS and higher grades of malignancy according to Patnaik (P = 0.002) and Kiupel (P < 0.001) grading systems. Cox-2 intensity was also associated with higher Ki-67 scores (P = 0.009), higher mitotic index (P = 0.022) and higher microvascularization density (P = 0.045). No association was observed for COX-2 intensity and CD3-T lymphocyte (P = 0.377) and macrophage infiltration (P = 0.261) by MAC-387 immunollabelling, suggesting an active role of COX-2 in MCT oncogenesis mainly through proliferation and angiogenesis stimulation making it a potentially clinical relevant prognosis marker and therapeutic target. Keywords angiogenesis, Cox-2, dog, inflammatory infiltrate, mast cell tumours, prognosis, proliferation Introduction Mast cell tumours (MCTs) are a common neoplasia in dogs and the most prevalent skin neoplasia in this specie. 1 – 4 No sex predisposition has been recorded but some specifc breeds such as Boxer, Weimaraner and Labrador appear to have an increased disease prevalence. 5 Tese tumours constitute a clinical challenge due to their wide spectrum of disease presentation ranging from non-aggressive, slow growing and indolent local disease to an aggres- sive and metastatic variant. 6,7 Although surgical treatment continues to be considered the main- stay treatment modality and usually curative in a large proportion of cases, other adjuvant treatment modalities are required for more aggressive dis- ease types. 7,8 Hence, prognostic information is of paramount importance for the clinician to plan for adequate treatment options. Histological grade, 5,9 clinical staging, 10,11 breed, 12 anatomic location 13,14 and proliferation markers 15 – 19 are routinely used to try to ascertain individual clinical behaviour, but no single one Correspondence address: F. L. Queiroga Department of Veterinary Sciences University of Trás-os-Montes and Alto Douro Quinta dos Prados 5001-801 Vila Real Portugal e-mail: fqueirog@utad.pt © 2016 John Wiley & Sons Ltd 1