VEGF and bFGF are highly expressed in intraluminal fibromyxoid lesions in bronchiolitis obliterans organizing pneumonia

J Pathol. 2002 Feb;196(2):220-7. doi: 10.1002/path.1038.


Bronchiolitis obliterans organizing pneumonia (BOOP) and usual interstitial pneumonia (UIP) are fibrous pulmonary disorders in which new fibromyxoid connective tissue is formed in distal air spaces. In BOOP this tissue is susceptible to even complete reversal, but in UIP it participates in the remodelling of the interstitium. Our previous study showed that in BOOP this newly formed intraluminal tissue is more capillarized than in UIP. This paper studies the immunohistochemical expression of vascular endothelial growth factor (VEGF) and its receptors Flt-1 and Flk-1, and basic fibroblast growth factor (bFGF) in BOOP and UIP. It was hypothesized that there would be a difference in the expression of these angiogenic growth factors paralleling the difference in their capillarization. The results show that both VEGF and bFGF are widely expressed in BOOP and in UIP. It was shown with two different VEGF antibodies that its expression was more pronounced in the intraluminal fibromyxoid lesions in BOOP than in UIP (p<0.001 and 0.004, respectively). Similarly, bFGF also showed stronger espression in BOOP than in UIP (p<0.02) in these areas. The expression of Flt-1 and Flk-1 was in agreement with the expression of VEGF. It is concluded that the growth factors VEGF and bFGF may have an important role in the pathogenesis of BOOP and UIP; furthermore, their expression correlates with the angiogenic activity of the newly formed intraluminal fibromyxoid connective tissue in BOOP. Angiogenesis mediated by these growth factors may be one reason for the reversal of intraluminal fibromyxoid connective tissue in BOOP and for its good clinical outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cryptogenic Organizing Pneumonia / metabolism*
  • Cryptogenic Organizing Pneumonia / pathology
  • Endothelial Growth Factors / analysis
  • Endothelial Growth Factors / metabolism*
  • Extracellular Matrix Proteins / analysis
  • Extracellular Matrix Proteins / metabolism
  • Fibroblast Growth Factor 2 / analysis
  • Fibroblast Growth Factor 2 / metabolism*
  • Humans
  • Immunohistochemistry / methods
  • Lung / pathology
  • Lymphokines / analysis
  • Lymphokines / metabolism*
  • Neovascularization, Pathologic
  • Pulmonary Fibrosis / metabolism*
  • Pulmonary Fibrosis / pathology
  • Receptor Protein-Tyrosine Kinases / analysis
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Growth Factor / analysis
  • Receptors, Growth Factor / metabolism
  • Receptors, Vascular Endothelial Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-1
  • Vascular Endothelial Growth Factors


  • Endothelial Growth Factors
  • Extracellular Matrix Proteins
  • Lymphokines
  • Receptors, Growth Factor
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Fibroblast Growth Factor 2
  • FLT1 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor
  • Vascular Endothelial Growth Factor Receptor-1