Vascular endothelial growth factor, platelet-derived endothelial cell growth factor and angiogenesis in non-small-cell lung cancer.
High microvessel density, an indirect measure of angiogenesis, has been shown to correlate with increased tumour size, lymph node involvement and poor prognosis in non-small-cell lung cancer (NSCLC). Tumour cell vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF) expression correlate with angiogenesis and a poor outcome in this disease. In a retrospective study VEGF and PD-ECGF expression and microvessel density were evaluated immunohistochemically in surgically resected specimens (T1-3, N0-2) from 223 patients with operable NSCLC using the VG1, P-GF.44C and JC70 monoclonal antibodies respectively. High VEGF immunoreactivity was seen in 104 (46.6%) and PD-ECGF in 72 (32.3%) cases and both were associated with high vascular grade tumours (P= 0.009 and P= 0.05 respectively). Linear regression analysis revealed a weak positive correlation between VEGF and PD-ECGF expression in cancer cells (r= 0.21; P = 0.002). Co-expression of VEGF and PD-ECGF was not associated with a higher microvessel density than VEGF or PD-ECGF only expressing tumours. Furthermore a proportion of high vascular grade tumours expressed neither growth factor. Univariate analysis revealed tumour size, nodal status, microvessel density and VEGF and PD-ECGF expression as significant prognostic factors. Tumour size (P < 0.02) and microvessel density (P < 0.04) remained significant on multivariate analysis. In conclusion, VEGF and PD-ECGF are important angiogenic growth factors and have prognostic significance in NSCLC. Furthermore the study underlines the prognostic significance of microvessel density in operable NSCLC.
O'Byrne
K J
KJ
University Department of Oncology, Leicester Royal Infirmary, UK.
Koukourakis
M I
MI
Giatromanolaki
A
A
Cox
G
G
Turley
H
H
Steward
W P
WP
Gatter
K
K
Harris
A L
AL
D000230:Adenocarcinoma / Q000098:blood supply / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000704:Analysis of Variance; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000201:enzymology / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000401:mortality / Q000473:pathology / Q000601:surgery; D016228:Endothelial Growth Factors / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000098:blood supply / Q000201:enzymology / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008222:Lymphokines / Q000032:analysis*; D008833:Microcirculation / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology*; D015588:Observer Variation; D011379:Prognosis; D020033:Protein Isoforms / Q000032:analysis; D016019:Survival Analysis; D013939:Thymidine Phosphorylase / Q000032:analysis*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013939:Thymidine Phosphorylase