The 'angiogenic switch' in the progression from Barrett's metaplasia to esophageal adenocarcinoma

Eur J Surg Oncol. 2003 Dec;29(10):890-4. doi: 10.1016/j.ejso.2003.07.002.


Aims: We investigated VEGF expression and neovascularisation in the metaplasia-dysplasia-carcinoma sequence of Barrett's esophagus and 47 shades of adenocarcinoma.

Method: Slides of 27 cases of Barrett's metaplasia and high grade dysplasia were immunostained for VEGF, CD 31 and alpha-sm actin to discriminate between mature and immature vessels. VEGF stained slides were quantitatively evaluated measuring optical density with a computer based program. The neovascularisation coefficient was estimated with an interactive analytic computer program.

Results: The median VEGF expression increased from metaplasia to advanced carcinoma. VEGF expression and the neovascularisation coefficient reached statistical significance between Barrett's metaplasia and high grade dysplasia (p<0.001), but were not statistically different between high grade dysplasia and microinvasive carcinoma (p=0.421; p=0.146). Comparing microinvasive to advanced carcinoma the difference was significant for both parameters (p<0.001).

Conclusions: Based on a quantitative computer based evaluation program, the present study suggests, that an angiogenic switch might exist and that it is an early event in the metaplasia-dysplasia-carcinoma sequence of Barrett's carcinoma. The neovascularisation phase in Barrett's carcinoma may precede tumour growth.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology*
  • Aged
  • Barrett Esophagus / metabolism*
  • Barrett Esophagus / pathology*
  • Disease Progression
  • Esophageal Neoplasms / metabolism*
  • Esophageal Neoplasms / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neovascularization, Pathologic
  • Precancerous Conditions / metabolism*
  • Statistics, Nonparametric
  • Vascular Endothelial Growth Factor A / metabolism*


  • Vascular Endothelial Growth Factor A