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

Vienna Ludovini, Vanesa Gregorc, Lorenza Pistola, Zhasmina Mihaylova, Irene Floriani, Samir Darwish, Fabrizio Stracci, Francesca Romana Tofanetti, Massimiliano Ferraldeschi, Luciana Di Carlo, Mark Ragusa, Giuliano Daddi, Maurizio Tonato

Research output: Contribution to journalArticle

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 (rs=0.26; P=0.015), positively with Bcl-2 (rs=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) (χ2=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.

Original languageEnglish
Pages (from-to)77-85
Number of pages9
JournalLung Cancer
Volume46
Issue number1
DOIs
Publication statusPublished - Oct 2004

Keywords

  • Biological factors
  • Cisplatin
  • Hemoglobin level
  • Lung cancer
  • Response to chemotherapy
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Ludovini, V., Gregorc, V., Pistola, L., Mihaylova, Z., Floriani, I., Darwish, S., Stracci, F., Tofanetti, F. R., Ferraldeschi, M., Di Carlo, L., Ragusa, M., Daddi, G., & Tonato, M. (2004). Vascular endothelial growth factor, p53, Rb, Bcl-2 expression and response to chemotherapy in advanced non-small cell lung cancer. Lung Cancer, 46(1), 77-85. https://doi.org/10.1016/j.lungcan.2004.03.018