Background: Vascular endothelial growth factor (VEGF), a specific mitogen for endothelial cells in vitro, can be angiogenic factor in vivo. VEGF is known to be produced by several tumor cells and plays an important role for neovascularization in tumor tissue. Recently, tyrosine kinase encoded by the flt gene was identified as a receptor for VEGF. Angiosarcoma (AS) is a rare malignant tumor that arises from endothelium. At present, little is known about a mechanism of proliferation of the AS.
Experimental design: In an immunohistochemical study of 99 cases of AS, 11 cases showing a positive reaction for anti-VEGF Ab were selected for the present study. In these cases, expression of VEGF and its receptor (flt) mRNA was examined by in situ hybridization: sense and antisense probes for VEGF and flt mRNA were used.
Results: In situ hybridization study with antisense probes revealed that the VEGF mRNA was expressed in AS cells and mononuclear cells in all but one case. Intensity of VEGF staining by immunohistochemistry correlated well with VEGF mRNA expression. The flt mRNA was expressed in AS cells in all 10 cases that were positive for VEGF mRNA. Sense probe for VEGF and flt mRNA gave no positive reactions.
Conclusions: These findings suggest a presence of paracrine or autocrine mechanism of proliferation in AS through VEGF and its receptor flt.