Pilot assessment of vascular endothelial growth factor receptors and trafficking pathways in recurrent and metastatic canine subcutaneous mast cell tumours

Vet Med Sci. 2017 Jun 30;3(3):146-155. doi: 10.1002/vms3.66. eCollection 2017 Aug.

Abstract

Canine subcutaneous mast cell tumour (scMCT) shows less aggressive biological behaviour than cutaneous MCT. Vascular endothelial growth factor receptor 2 (VEGFR2) is expressed by neoplastic cells in canine scMCT, but the relevance of this signalling pathway for disease pathobiology is not clear. The objective of this study was to quantify VEGF-A, VEGFR2, pVEGFR2, the VEGF co-receptor Neuropilin 1 (NRP-1) and the E3 ubiquitin protein ligase c-Cbl in canine scMCT, and to evaluate their association with disease outcome. Immunohistochemical staining for biomarkers was quantified from 14 cases of canine scMCT using manual and computer-assisted methods. Kaplan-Meier curves were generated for disease-free survival (DFS) and compared using Mantel-Cox log-rank analysis. Cases with high levels of neoplastic cell VEGFR2, pVEGFR2 or c-CBL immunoreactivity had significantly reduced DFS. All cases displayed neoplastic cells positive for VEGF-A, which was significantly associated with pVEGFR2 immunoreactivity. There were also significant positive correlations between VEGFR2 and pVEGFR2, and between c-CBL and pVEGFR2 levels. This pilot study demonstrates the potential utility of these markers in a subset of scMCT in dogs.

Keywords: Neuropilin‐1; VEGFR2; c‐CBL; dog.