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

Introduction: We evaluated the prognostic impact of tumor angiogenesis assessed by vascular endothelial growth factor (VEGF), microvessel density (MVD), and tumor vessel invasion in patients who underwent radical resection for stage IB-IIA non-small cell lung cancer (NSCLC). Materials and Methods: Fifty-one patients (42 males and 9 females, mean age 62.3 +/- 6.9) undergoing complete surgical resection (lobectomy n=35, pneumonectomy n=16) of pathologic stage IB (n=43) and IIA (n=8) NSCLC were retrospectively evaluated. No patient underwent postoperative chemotherapy or neoadjuvant therapy. Minimum follow-up period for surviving patients was 36 months (mean 46.9 +/- 35.5). Paraffin embedded tumor specimens were stained for VEGF and specific MVD markers: CD31, CD34 and CD105. VEGF overexpression was certified when more than 25% of carcinoma cells were stained. CD31, CD34, CD105 were evaluated per high power field at 400x magnification; median values were chosen as cutoff points. Tumor vessel invasion was assessed after staining by CD34. Results: Five-year Kaplan-Meier survival rate significantly correlated with VEGF overexpression (39% Vs 88%, p=0.003), high CD34 (33% Vs 74%, p=0.005), high CD105 (38% Vs 76%, p=0.03), and invasion (30% Vs 58%, p=0.02). Age, sex, histology, grading and CD31 were not significant. Multivariate analysis selected high CD34 (p=0.007, OR=3.5, CI95%=1.4-8.7) and invasion (p=0.02, OR=2.8, CI95%=1.1-6.9). The simultaneous presence of such factors was highly predictive of poor outcome (p=0.0002, OR=3.4, CI95%=1.7-6.5). Conclusions: High MVD by CD34 and tumor vessel invasion are more related to poor survival than the other neoangiogenetic factors in stage IB-IIA NSCLC.