Title: 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: The expression of 5 markers associated with angiogenesis was studied in canine squamous cell carcinomas (SCCs) ( n = 19) and canine trichoepitheliomas (TCPs) ( n = 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 2′-deoxyuridine 5′-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 = 0.51); and moderate correlation between VEGF and histologic grade ( r = 0.43), VEGFR-2 and histologic grade ( r = 0.47), VEGF and PI ( r = 0.47), and VEGFR-2 and PI ( r = 0.47) (Spearman rank correlation coefficient). In TCPs, there was substantial correlation between VEGF and PI ( r = 0.51) and a moderate correlation between VEGFR-2 and iMVD ( r = 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.