Tumor angiogenesis and recurrence in stage I non-small cell lung cancer

Ann Thorac Surg. 1999 Sep;68(3):1034-8. doi: 10.1016/s0003-4975(99)00611-6.


Background: Tumor angiogenesis appears to relate to recurrence after an operation as a route for distant metastasis. We assessed the association of vascular endothelial growth factor (VEGF) expression and intratumoral microvessel density (MD) with recurrence in primary lung cancer.

Methods: Samples were randomly obtained from 104 stage I lung cancer patients who underwent curative operations (43 recurrent, 61 nonrecurrent patients). Microvessels were highlighted by staining endothelial cells for factor VIII and VEGF antigen was detected using a polyclonal antibody.

Results: VEGF antigen was detected in large amounts in both recurrent (100%) and nonrecurrent tumors (73.8%). The percentages of patients with the strongest VEGF stain (more than 50% of staining area in tumor cells) were 46.5% in tumors with recurrence and 11.5% in tumors without recurrence. The mean MD in recurrent and nonrecurrent tumors were 18.2+/-10.5 and 8.5+/-5.0, respectively, resulting in a significantly greater value in tumors with recurrence (p<0.0001). Although there were no significant differences in mean MD according to pathological types, in adenocarcinoma and adenosquamous carcinoma, the mean value in the recurrent group was significantly greater than that in the nonrecurrent one.

Conclusions: An evaluation of VEGF expression and MD in tumors may contribute to the estimation of the risk of recurrence of non-small cell lung cancer in early stages.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / blood supply*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Endothelial Growth Factors / analysis
  • Factor VIII / analysis
  • Female
  • Humans
  • Lung Neoplasms / blood supply*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Lymphokines / analysis
  • Male
  • Microcirculation / metabolism
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neovascularization, Pathologic*
  • Random Allocation
  • Risk Factors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Factor VIII