What is the clinical significance of stromal angiogenesis in Barrett's esophagus?
BACKGROUND
Enriched blood vessels occur in the stroma of Barrett's esophagus and are related to the ease of tumor invasion in the early stage of the cancer. Hypoxia-inducible factor (HIF) is closely related with angiogenesis through expression of vascular endothelial growth factor. The aim of the present study was to determine the predictors for angiogenesis in Barrett's esophagus and evaluate their clinical significance.


METHODS
Between December 2003 and May 2004, 209 patients with endoscopically and histologically proven Barrett's esophagus were enrolled. Before endoscopic examination, all participants answered structured questionnaires for gastroesophageal reflux symptoms and drug usage. HIF-1alpha and COX-2 protein expressions, cellular proliferation, and apoptosis were investigated immunohistochemically in biopsy samples taken from the esophagus of each patient. The degree of angiogenesis was determined by CD34 immunostaining analysis. Predictors for angiogenesis were evaluated with multivariate logistic regression analysis.


RESULTS
Sixty (28.7%) of the 209 enrolled patients with Barrett's esophagus had a high CD34 score. Factors proven as positive predictors for a high CD34 score were presence of gastroesophageal reflux symptoms, reflux esophagitis, COX-2 protein expression, and the proliferating cell nuclear antigen (PCNA) index. Administration of proton-pump inhibitors and HIF-1alpha protein expression were not predictors.


CONCLUSIONS
Reflux esophagitis and gastroesophageal reflux symptoms were positive predictors for enriched angiogenesis in the stromal portion of Barrett's esophagus, which has malignant potential because the epithelial cells express COX-2 and have accelerated cellular proliferation.
Moriyama
Nobuyuki
N
Department of Gastroenterology and Hepatology, Shimane University, School of Medicine, Izumo-shi, Shimane Japan.
Amano
Yuji
Y
Mishima
Yuko
Y
Okita
Koichi
K
Takahashi
Yoshiko
Y
Yuki
Takafumi
T
Ishimura
Norihisa
N
Ishihara
Shunji
S
Kinoshita
Yoshikazu
Y
D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis; D001471:Barrett Esophagus / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000032:analysis; D004942:Esophagitis, Peptic / Q000473:pathology / Q000503:physiopathology; D004945:Esophagoscopy; D005260:Female; D005764:Gastroesophageal Reflux / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D007150:Immunohistochemistry; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D016017:Odds Ratio; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D018570:Risk Assessment; D012307:Risk Factors; D017154:Stromal Cells / Q000737:chemistry / Q000473:pathology*
D018952:Antigens, CD34; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018809:Proliferating Cell Nuclear Antigen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human