The ‘angiogenic switch’ in the progression from Barrettʹs metaplasia to esophageal adenocarcinoma

Aims: We investigated VEGF expression and neovascularisation in the metaplasia–dysplasia–carcinoma sequence of Barrettʹs esophagus and 47 shades of adenocarcinoma. Method: Slides of 27 cases of Barrettʹs metaplasia and high grade dysplasia were immunostained for VEGF, CD 31 and α-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 Barrettʹs 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 Barrettʹs carcinoma. The neovascularisation phase in Barrettʹs carcinoma may precede tumour growth.