Vascular endothelial growth factor, p53, Rb, Bcl-2 expression and response to chemotherapy in advanced non-small cell lung cancer.

Abstract Vascular endothelial growth factor (VEGF) increases microvascular permeability and stimulates endothelial cell growth. p53 Overexpression has been associated with resistance to cisplatin-based chemotherapy in patients (pts) with NSCLC. The aim of this study was to evaluate the predictive role of VEGF for chemotherapy response, its relationship with p53, Rb, Bcl-2 and hemoglobin levels and its impact on overall survival in pts with advanced NSCLC. Bronchial or fine-needle biopsy specimens from 85 pts with NSCLC obtained before chemotherapy were analyzed using an immunohistochemical method for VEGF, p53, Rb and Bcl-2. There were 73 males and 12 females with a median age of 62.6 years. The majority of pts (48%) had squamous cell histology. Ten pts had stage IIIA, 25 stage IIIB and 50 stage IV. Thirty six (43%) pts had positive immunostaining for VEGF, 37 (44%) had positive p53, 53 (62%) had negative Rb and 4 (5%) had positive Bcl-2. VEGF was negatively correlated with Rb ( r s =0.26; P =0.015), positively with Bcl-2 ( r s =0.22; P =0.042), whereas no statistically significant correlation with p53, age, stage and histological type was found. In a logistic regression model, adjusting for treatment, VEGF expression was not associated with chemotherapy response (odds ratio (OR)=1.01; P =0.085), unlike p53 positivity and Rb negativity (OR=4.0, P =0.005; OR=2.6, P =0.016, respectively). A statistically significant higher VEGF expression was detected in the subgroups defined, using as cut-off value Hb median level (13.3 g/dl) ( χ 2 =5.00; one d.f.; P =0.025). At a median follow-up time of 8.4 years, 2-year survival was 21%. After adjustment for stage and chemotherapy treatment, VEGF expression was not associated with a better overall survival (OR=1.06; P =0.80), unlike Bcl-2 positivity showed a statistically significant effect (OR=0.28; P =0.02). Our results suggest that VEGF is weakly correlated with regulators of apoptosis and has not been shown to be an independent predictive factor for resistance to cisplatin-based chemotherapy and prognostic for survival.