Prognostic impact of VEGF, CD31, CD34, and CD105 expression and tumour vessel invasion after radical surgery for IB-IIA non-small cell lung cancer

Abstract

Aims: To evaluate the prognostic impact of tumour angiogenesis assessed by vascular endothelial growth factor (VEGF), microvessel density (MVD), and tumour vessel invasion in patients who had undergone radical resection for stage IB-IIA non-small cell lung cancer (NSCLC).

Methods: Fifty one patients (42 men, nine women; mean age, 62.3 years; SD, 6.9) undergoing complete surgical resection (35 lobectomy, 16 pneumonectomy) of pathological stage IB (n = 43) and IIA (n = 8) NSCLC were evaluated retrospectively. No patient underwent postoperative chemotherapy or neoadjuvant treatment. Tumour specimens were stained for VEGF and specific MVD markers: CD31, CD34, and CD105.

Results: VEGF expression significantly correlated with high CD105 expression (p < 0.0001) and tumour vessel invasion (p = 0.04). Univariate analysis showed that those patients with VEGF overexpression (p = 0.0029), high MVD by CD34 (p = 0.0081), high MVD by CD105 (p = 0.0261), and tumour vessel invasion (p = 0.0245) have a shorter overall survival. Furthermore, multivariate Cox regression analysis showed that MVD by CD34 (p = 0.007), tumour vessel invasion (p = 0.024), and VEGF expression (p = 0.042) were significant predictive factors for overall survival. Finally, the presence of both risk factors, tumour vessel invasion and MVD by CD34, was highly predictive of poor outcome (odds ratio, 3.4; 95% confidence interval, 1.7 to 6.5; p = 0.0002).

Conclusions: High MVD by CD34 and tumour vessel invasion are more closely related to poor survival than the other neoangiogenetic factors in stage IB-IIA NSCLC. This may be because these factors are more closely related to the metastatic process.

Figure 1

Representative immunostaining for (A) vascular endothelial growth factor, (B) CD31, (C) CD34, and (D) CD105.

Figure 2

Kaplan-Meier curve for the study population stratified for the various neovascularisation factors. (A) VEGF expression. The five year overall survival rate was 88% for low expression (⩽ 25%) and 39.2% for overexpression (> 25%). (B) Microvessel density (MVD) assessed by CD34. The five year overall survival rate was 69.6% for low (⩽ 130) and 29.5% for high (> 130) MVD. (C) MVD assessed by CD105. The five year overall survival rate was 76.5% for low (⩽ 60) and 37.7% for high (> 60) MVD. (D) Tumour vessel invasion. The five year overall survival rate was 30.9% when present and 60.9% when absent.

Figure 3

Kaplan-Meier curve for the study population for combined tumour vessel invasion and microvessel density as assessed by CD34. The five year overall survival rate was 77.3% for no positive factor, 43.2% for one positive factor, and 0% for two positive factors.