The clinical significance of lymphangiogenesis and angiogenesis in non-small cell lung cancer patients

Background: Angiogenesis and lymphangiogenesis have been reported to affect malignant phenotype. Method: We investigated 147 patients with non-small cell lung cancer (NSCLC). Immunohistochemistry using D2-40 was performed to evaluate lymphatic vessel density (LVD), including Micro-LVD (without lumen),Tubal-LVD (with lumen) and lymphatic vessel invasion (LVI). The intratumoural microvessel density (MVD) was evaluated by CD-34 immunostaining. The expressions of vascular endothelial growth factor-A (VEGF-A) and VEGF-C were also studied. Results: Lymphangiogenesis was significantly associated with Micro-LVD (p = 0.0003). The VEGF-C expression was significantly associated with the Micro-LVD (p = 0.0057). In contrast, the VEGF-A expression was significantly associated with the MVD (p = 0.0092). The survival was significantly lower in patients with Micro-LVD-high tumours than in patients with Micro-LVD-low tumours (p = 0.0397). Survival was also significantly lower in patients with MVD-high tumours than in patients with MVD-low tumours (p = 0.0334). A multivariate analysis demonstrated that the Micro-LVD (p = 0.0363) and the MVD (p = 0.0232) were independent prognostic factors for NSCLC patients. Conclusions: Lymphangiogenesis, specifically Micro-LVD and angiogenesis are independently associated with a poor prognosis in NSCLC patients. (c) 2008 Elsevier Ltd. All rights reserved.