Angiogenetic biomarkers in non-small cell lung cancer with malignant pleural effusion: correlations with patient survival and pleural effusion control

Lung Cancer. 2009 Sep;65(3):371-6. doi: 10.1016/j.lungcan.2008.12.007. Epub 2009 Jan 21.


Objective: To evaluate how the angiogenetic biomarkers vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and interleukin-8 (IL-8) in the fluid of non-small cell lung cancer (NSCLC) with malignant pleural effusion (MPE) correlate with patient survival and pleural effusion control.

Design: Prospective study.

Patients and methods: From April 1, 1998 to April 30, 2005, we used thoracoscopic biopsy to collect pleural specimens and pleural effusion from 97 patients with NSCLC and MPE. Paired blood samples were harvested. We used enzyme-linked immunosorbent assays to evaluate levels of angiogenic factors in MPE and blood, and immunohistochemical staining to evaluate them in pleural specimens. Related data, such as patient survival and PE control, were collected for correlation analysis.

Results: Smoking and PE VEGF >1350 ng/mL were both significant negative predictors of patient survival. A trapped lung was the only significant factor for poor PE control. The serum level, the amount of PE, and the number of red blood cells in PE correlated well with PE VEGF level. Immunohistochemical staining of pleural samples showed that VEGF was secreted by both mesothelial and tumor cells. The level of PE IL-8 weakly correlated with PE VEGF, and the level of bFGF was not significant.

Conclusions: PE VEGF was a useful angiogenetic factor for the amount of fluid in patients with NSCLC and MPE. In addition to smoking, PE VEGF >1350 ng/mL was a significant negative predictor of patient survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor*
  • Carcinoma, Non-Small-Cell Lung / blood supply*
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / physiopathology
  • Cell Count
  • Disease Progression
  • Epithelium / metabolism*
  • Epithelium / pathology
  • Erythrocytes
  • Fibroblast Growth Factor 2 / metabolism
  • Humans
  • Interleukin-8 / metabolism
  • Lung Neoplasms / blood supply*
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / physiopathology
  • Middle Aged
  • Neovascularization, Pathologic*
  • Prognosis
  • Smoking
  • Survival Analysis
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*


  • Biomarkers, Tumor
  • Interleukin-8
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2