Expression of Vascular Endothelial Growth Factor, Basic Fibroblast Growth Factor, and Their Receptors (Flt-1, Flk-1, and Flg-1) in Canine Vascular Tumors

Abstract

Expression of vascular endothelial growth factor (VEGF), its receptors (flt-1 and flk-1), and basic fibroblast growth factor (bFGF) in canine hemangiosarcoma (HSA) and hemangiomas was investigated by immunohistochemical analysis. In addition, expression of the mRNAs of VEGF, flt-1, flk-1, and flg-1 (a receptor for bFGF), was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) with cRNA probes. VEGF, bFGF, flt-1, and flk-1 were immunohistochemically detected in the neoplastic cells in HSAs; the staining intensity was stronger in HSAs than in hemangiomas. On the other hand, the neoplastic cells in hemangiomas exhibited very weak or no expression of VEGF, although they showed moderate expression of flt-1 and flk-1. The mRNAs of VEGF, flt-1, flk-1, and flg-1 were detected in the neoplastic cells in HSAs by ISH and RT-PCR. However, VEGF mRNA was not detectable in the neoplastic cells in hemangiomas by ISH, although it was detected in the inflammatory cells in the tumors by RT-PCR. Moreover, the HSAs that showed intense staining for flk-1 had a high proliferative activity, which was reflected as a high Ki-67 positive index. These results suggest that the expression of the growth factors and their receptors, especially flk-1, might be associated with the malignant proliferation of HSAs.