VEGF, VEGFR-1, VEGFR-2, microvessel density and endothelial cell proliferation in tumours of the ovary

VEGF is an angiogenic factor with potent endothelial cell (EC) proliferativ e actions. Our aim was to investigate whether expression of VEGF and its re ceptors and EC proliferation differ between ovarian tumour types and region s of the vasculature. VEGF, VEGFR-1, VEGFR-2 and EC proliferation were exam ined immuno-histochemically, and in situ hybridisation (ISH) studies of VEG F mRNA expression were performed and assessed in regions of high (HVD) and average (AVD) vessel density. VEGF immunostaining was significantly stronge r in HVD regions of malignant compared with borderline serous tumours. VEGF immunostaining did not differ between tumour types; however, the percentag e of VEGFR-1 and VEGFR-2-positive vessels was significantly lower in mucino us tumours. No differences were observed between HVD and AVD regions. VEGF ISH signal was observed in 2/7 borderline mucinous tumours, 8/14 malignant serous tumours and 5/13 benign tumours. The EC proliferation index was sign ificantly lower in the HVD regions of serous relative to benign tumours. A negative correlation between VEGFR-1 immunostaining and microvessel density was observed in benign and serous tumours. However, EC proliferation index and VEGFR-1 positivity were positively correlated in benign tumours. Our r esults suggest that VEGF may play a role in the control of angiogenesis in serous and benign tumours but it does not appear to contribute to the previ ously reported higher microvessel density in mucinous tumours or to influen ce heterogeneity of microvessel density in ovarian tumours. Int. J. Cancer (Pred. OncoL) 84: 101-108, 1999, (C) 1999 Wiley-Liss, Inc.