Hypoxia inducible factor-1 alpha and vascular endothelial growth factor in biopsies of small cell lung carcinoma

Lung. Sep-Oct 2009;187(5):321-9. doi: 10.1007/s00408-009-9169-z. Epub 2009 Aug 26.

Abstract

Neoangiogenesis has been documented in small cell lung carcinoma (SCLC). In addition, antiangiogenic therapies are being tested in clinical trials that involve SCLC. However, study of the underlying mechanisms has been performed almost exclusively in cell lines. In the current study, we immunostained 30 biopsy samples of SCLC with antibodies to hypoxia inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), vascular endothelial growth factor-receptor 1 (VEGF-R1/flt-1) and vascular endothelial growth factor-receptor 2 (VEGF-R1/flk-1). The immunoreactivity was analyzed using a bivariate Spearman correlation test and linear regression analysis. We found significant correlation between HIF-1 alpha nuclear staining and VEGF staining. Moreover HIF-1 alpha+/VEGF+ cases were associated with poor survival. We also found a positive correlation between VEGF and VEGF-R2 expression. We suggest that a HIF-1 alpha/VEGF angiogenic pathway may exist in vivo in SCLC, similar to that in non-SCLC. Our data also suggest a potential VEGF/VEGFR-2 autocrine pathway in SCLC. The inclusion of novel inhibitors to HIF-1 alpha and other factors may optimize antiangiogenic interventions in SCLC.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biopsy
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / analysis*
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Linear Models
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / chemistry*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Proportional Hazards Models
  • Risk Assessment
  • Small Cell Lung Carcinoma / blood supply
  • Small Cell Lung Carcinoma / chemistry*
  • Small Cell Lung Carcinoma / mortality
  • Small Cell Lung Carcinoma / pathology
  • Small Cell Lung Carcinoma / therapy
  • Time Factors
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / analysis*
  • Vascular Endothelial Growth Factor Receptor-1 / analysis
  • Vascular Endothelial Growth Factor Receptor-2 / analysis

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factor Receptor-2