ASSOCIATION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR EXPRESSION WITH INTRATUMORAL MICROVESSEL DENSITY AND TUMOR-CELL PROLIFERATION IN HUMAN EPIDERMOID LUNG-CARCINOMA

Vascular endothelial growth factor (VEGF) expression, vascularisation and tumour cell proliferation were analysed in 91 human epidermoid lun g carcinomas using immunohistochemistry. A polyclonal anti-VEGF antibo dy was used for VEGF expression, a polyclonal antibody directed agains t human von Willebrand factor (factor VIII) to identify blood vessels and the proliferating cell nuclear antigen (PCNA) as a marker for prol iferating cells. Positive staining for VEGF was obtained in 54 out of 91 cases (59%), the number of blood vessels varied from zero to 64 cou nts (mean 9.4) and the proportion of PCNA-positive cells varied from 1 .3% to 72.1% (mean 25.2%). The mean PCNA labelling index and mean micr ovessel count in VEGF-positive tumours were significantly higher than those in VEGF-negative tumours (Wilcoxon rank sum test, P<0.0001; P<0. 05). In addition, PCNA labelling index significantly increased with in creasing VEGF expression (Jonckheere test, P<0.0001). In contrast, no association was found between PCNA labelling index and tumour vascular ity (r=0.07, P=0.48). The close correlation of VEGF expression with tu mour cell proliferation and microvessel density suggests that VEGF act s both as an autocrine growth factor and as stimulator for angiogenesi s. However, tumour cell proliferation and microvessel growth and/or de nsity may be regulated by separate mechanisms.