The 'angiogenic switch' in the progression from Barrett's metaplasia to esophageal adenocarcinoma.
OBJECTIVE
We investigated VEGF expression and neovascularisation in the metaplasia-dysplasia-carcinoma sequence of Barrett's esophagus and 47 shades of adenocarcinoma.


METHODS
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.
Möbius
C
C
Department of Surgery, Klinikum rechts der Isar der TU Munchen, Munchen, Germany.
Stein
H J
HJ
Becker
I
I
Feith
M
M
Theisen
J
J
Gais
P
P
Jütting
U
U
Siewert
J R
JR
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000368:Aged; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011230:Precancerous Conditions / Q000378:metabolism*; D018709:Statistics, Nonparametric; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A