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.