Vascular endothelial growth factor/KDR activated microvessel density versus CD31 standard microvessel density in non-small cell lung cancer

Vascular endothelial growth factor (VEGF) is an important angiogenic factor , linked to poor outcome in human malignancies including non-small cell lun g carcinoma (NSCLC). We used the 11B5 monoclonal antibody recognizing the V EGF/KDR complex (R. A. Brekken et al., Cancer Res., 58: 1952-1959, 1998) to assess the VEGF expression in cancer cells and the VEGF/KDR activated micr ovessel density (aMVD) in early operable NSCLC. The JC70 anti-CD31 monoclon al antibody was used to assess the standard MVD (sMVD). The aMVD was signif icantly higher in the invading front of the tumors and in the normal lung a djacent to the tumors as compared with normal lung distant to the tumor or to inner tumor areas (P < 0.0002). The sMVD was higher in the normal lung a nd decreased from the invading front to inner tumor areas (P < 0.0001). How ever, the vascular activation (aMVD:sMVD) was 4-6 times higher in the tumor areas as compared with lung from normal individuals (36-58% versus 9%; P < 0.0001). Fibroblast 11B5 reactivity, noted in 25% of cases, correlated wit h high aMVD and sMVD in the inner tumor areas. Multivariate analysis showed that aMVD was the most potent and independent prognostic factor (P = 0.001 ; t-ratio, 3.28). It is concluded that intense VEGF/KDR angiogenic pathway activation is a tumor-specific feature in more than 50% of NSCLC cases and is associated with poor postoperative outcome. Clinical trials involving ta rgeting of the VEGF/KDR-positive vasculature with specific antibodies, such as 11B5, are, therefore, encouraged.