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

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 46; no. 1; pp. 77 - 85
• Main Authors: Ludovini, Vienna, Gregorc, Vanesa, Pistola, Lorenza, Mihaylova, Zhasmina, Floriani, Irene, Darwish, Samir, Stracci, Fabrizio, Tofanetti, Francesca Romana, Ferraldeschi, Massimiliano, Di Carlo, Luciana, Ragusa, Mark, Daddi, Giuliano, Tonato, Maurizio
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.10.2004; Elsevier Science
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biological factors; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cisplatin; Female; Hemoglobin level; Humans; Immunohistochemistry; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Neoplasm Staging; Pneumology; Prognosis; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Response to chemotherapy; Retinoblastoma Protein - biosynthesis; Survival Analysis; Treatment Outcome; Tumor Suppressor Protein p53 - biosynthesis; Tumors of the respiratory system and mediastinum; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - biosynthesis; Response to chemotherapy; Hemoglobin level; Vascular endothelial growth factor; Lung cancer; Biological factors; Cisplatin; Antineoplastic agent; Lung disease; Respiratory disease; Biology; Malignant tumor; non-small cell lung carcinoma; Gene expression; Bronchopulmonary malignant tumor; Chemotherapy; Vascular endothelium growth factor; TP53 Gene; Treatment; Hemoglobin; Bronchus disease; Non small cell carcinoma; Tumor suppressor gene
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2004.03.018

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.