Immunohistochemical Expression of Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor Associated with Tumor Cell Proliferation in Canine Cutaneous Squamous Cell Carcinomas and Trichoepitheliomas

Abstract

Abstract. The expression of 5 markers associated with angiogenesis was studied in canine squamous cell carcinomas (SCCs) (n 5 19) and canine trichoepitheliomas (TCPs) (n 5 24). SCCs were assigned histologic grades, and tissue sections from both tumor types were immunohistochemially stained for the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2), as well as intratumoral microvessel density (iMVD), tumor proliferation index (PI), and tumor apoptotic index (AI), using antibodies against VEGF, VEGFR-2, von Willebrand's factor, Ki-67 antigen, and the terminal deoxynucleotidyl transferase-mediated 29-deoxyuridine 59-triphosphate endlabeling method (TUNEL), respectively. VEGF and VEGFR-2 were detected in 17/19 (89.4%) and 19/19 (100%) SCCs and in 17/24 (70.8%) and 20/24 (83.3%) TCPs, respectively. In SCCs, there was substantial correlation between histologic grade and PI (r 5 0.51); and moderate correlation between VEGF and histologic grade (r 5 0.43), VEGFR-2 and histologic grade (r 5 0.47), VEGF and PI (r 5 0.47), and VEGFR-2 and PI (r 5 0.47) (Spearman rank correlation coefficient). In TCPs, there was substantial correlation between VEGF and PI (r 5 0.51) and a moderate correlation between VEGFR-2 and iMVD (r 5 0.36). The median iMVD of SCCs (15.5) was significantly higher than the median iMVD of TCPs (9.05) (P value , .05). It was concluded that VEGF and VEGFR-2 may promote tumor cell proliferation in TCPs and SCCs. An autocrine pathway for VEGF probably operates in canine SCCs and TCPs, as VEGF and VEGFR-2 expression was found in most tumors and was associated with evidence for tumor cell proliferation.

Immunohistochemical expression of vascular endothelial growth factor in canine oral squamous cell carcinomas

“…The activation of VEGFR-1 promotes endothelial cell migration, but does not induce cell proliferation (30)(31)(32). However, VEGFR-2 is the major mediator of endothelial cell proliferation and survival, and it is also essential for the differentiation of endothelial cells and the induction of microvessel permeability (11,33).…”

“…Angiogenic switch is determined by the net balance of natural inhibitors and angiogenic stimulators, out of which vascular endothelial growth factor (VEGF), also termed VEGF-A, is considered to be the major stimulator responsible for tumour angiogenesis (6,7). Although extensive data are available on the role of VEGF and VEGF receptors in the biology and development of a variety of human and animal invasive malignant tumours (8)(9)(10)(11)(12)(13)(14), little information exists concerning oral canine tumours (15).…”

An Investigation of Growth Factors and Lactoferrin in Naturally Occurring Ovine Pulmonary Adenomatosis

“…VEGF is a specific mitogen for vascular endothelial cells and is produced by various cell types including macrophages and tumour cells (Yoshiji et al, 1996;Birck et al, 1999;Kiriakidis et al, 2003). Elevated VEGF signalling has been correlated with the histological grade of human (Du et al, 2003) and animal tumours (Maiolino et al, 2000;Millanta et al, 2002Millanta et al, , 2006Millanta et al, , 2010Al-Dissi et al, 2007).…”

Angiogenesis in Spontaneous Tumors and Implications for Comparative Tumor Biology

“…Only two studies examined the expression of VEGF in canine cutaneous SCC. The expression of VEGF was found in the majority of SCCs in both studies [78, 79]. Both studies also reported an increase in VEGF expression level with the advancement of histological grade with one study reporting higher levels in SCC arising on the toe [78].…”