Aspects regarding intratumor angiogenesis and vasculogenic mimicry in canine mammary tumors

Canine mammary tumors represent an important cause of morbidity and mortality in female dogs worldwide having a three times higher frequency than breast cancer in women. Neo-angiogenesis is critical for tumor growth, progression and metastases. The purpose of this study was to investigate neo-angiogenesis in canine mammary tumors and its possible utility as a prognostic biomarker by comparison with classic prognostic factors. In addition, we investigated if vasculogenic mimicry phenomenon of intratumor angiogenesis exists in this tumor type. Paraffin-embedded tissue samples from 21 female dogs with mammary cancers were immunostained for CD31 and Ki-67 nuclear proliferation marker, using Dako LSAB (Labelled streptavidin biotin)+System-HRP (Horseradish Peroxidase). Vasculogenic mimicry pattern was detected where necessary by double staining procedure. Statistical analysis was performed in Statistica software, p<0.05. We obtained a progressive increase of IMD (intratumor microvessel density) in poorly differentiated mammary carcinomas with high proliferative rate, comparing with differentiated ones (p<0.0001). The occurrence of blood channels was higher in vicinity of intratumor necrotic areas. Vasculogenic mimicry was observed more often in tumors with reduced stroma and numerous cancerous cells (such as solid mammary carcinomas), and in poorly differentiated canine mammary cancer There was a statistical correlation between VM (vasculogenic mimicry) incidence and tumoral grade (p<0.0001). An increased incidence of VM was noticed in canine mammary carcinomas with high rate of intratumoral neo-angiogenesis showed by elevated IMD values (p<0.0007). Evaluation of neo-angiogenesis represents an additional factor that promotes the aggressiveness of canine mammary tumors, allowing the selection of a group of tumors with an aggressive behavior that generate vascular channels which facilitate tumor perfusion.