Canine Cutaneous Haemangiosarcoma: Biomarkers and Survival

Abstract

Haemangiosarcoma (HSA) is a malignant tumour of vascular endothelial cells. It is common in dogs, but rare in other species, and may arise in any tissue. A dermal location of canine HSA has been associated with short survival and recurrence after surgical excision. Solar radiation has been proposed as a predisposing factor in shorthaired dogs with light skin pigmentation. There are no studies relating the expression of immunohistochemical markers to survival of dogs with cutaneous haemangiosarcoma (cHSA). Such data could contribute to establishing prognostic factors and new therapies based on the expression of target molecules. The aim of this study was to evaluate biomarkers and overall survival (OS) of dogs with cHSA, therefore helping to understand the biological behaviour of this neoplasm and determine prognostic factors. Sixty samples of canine cHSA were evaluated for the expression of factor VIII (FVIII), cyclo-oxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA) and caspase-3 (Casp-3) by immunohistochemistry. The results were related to OS of animals through the model of competitive risks. In addition, the relationships between age, sex, breed, tumour invasiveness, histological differentiation scoring, mitotic rate and tumour size were correlated with the OS of the dogs. Markers expression was positive in 80-100% of the samples, predominantly with weak to moderate labelling intensity for FVIII, COX-2, and VEGF, but with strong expression of PCNA and Casp-3. The median OS of dogs was 12 months. The variables of dog age, tumour invasiveness, histological differentiation scoring, mitotic rate and tumour size were not related to the survival rate. Some predisposed breeds (i.e. pitbull, boxer, Basset hound and Dalmatian) showed greater OS than non-predisposed breeds. Dogs affected by other concomitant primary neoplasms had a longer survival curve than those with only cHSA, while the females of the former group had lower OS than males. The labelling indices of FVIII, COX-2, VEGF, PCNA and Casp-3 had no relationship to OS, neither did the labelling intensity of FVIII, COX-2 and VEGF. However, the expression of COX-2 and VEGF is frequent in canine cHSA so these possible therapeutic targets should be investigated further.

Keywords: cutaneous haemangiosarcoma; dog; immunohistochemistry; prognosis.