Vascular endothelial growth factor, wild-type p53, and angiogenesis in early operable non-small cell lung cancer

Vascular endothelial growth factor (VEGF) is a cytokine that is involved in tumor angiogenesis, Wild-type p53 (wt-p53) protein has been shown in cell lines to suppress angiogenesis through thrombospondin regulation. In this s tudy, we immunohistochemically examined the expression of VEGF, nuclear and wild-type cytoplasmic p53, bcl-2, epidermal growth factor receptor, and c- erbB-2 oncoprotein; vascular grade; proliferation index; and extent of necr osis in non-small cell lung cancer (NSCLC), We analyzed 120 cases of early- stage NSCLCs (81 squamous cell carcinomas and 39 adenocarcinomas) treated w ith surgery alone (median follow-up, 63 months; range, 45-74 months). VEGF expression showed a positive association with high vascular grade (microves sel score of >75 per x250 field; P = 0.008), although about half of the LVG cases also expressed VEGF. None of the p53 antibodies examined correlated with angiogenesis. However, wt-p53 expression was inversely associated with VEGF expression, suggesting that wt-p53 is involved in the suppression of the VEGF gene. Combined analysis of VEGF, wt-p53, and microvessel counting showed that, although wt-p53 loss associates with VEGF switch-on, p53 prote in may not be involved in the regulation of the angiogenic events downstrea m of VEGF expression. Moreover, no significant association of bcl-2 and c-e rbB-2 oncoprotein expression,vith VEGF expression was observed. T/N stage, grade, Ki67 proliferation index, and extent of necrosis were not correlated with VEGF expression. Survival analysis showed that VEGF correlated with p oor survival (P = 0.04) and was significant in node-negative cases (P = 0.0 3). We conclude that VEGF is an important angiogenic factor in NSCLC, its e xpression being dependent on wt-p53 loss.