COX-2 mRNA expression is significantly increased in acid-exposed compared to nonexposed squamous epithelium in gastroesophageal reflux disease.
BACKGROUND
Little is known about the role of cyclooxygenase (COX)-2 in gastroesophageal reflux disease (GERD) and the development of Barrett's metaplasia. The objectives of this study were to further analyze COX-2 mRNA expression in patients with GERD compared to Barrett's esophagus (BE) and Barrett's cancer (BC).


METHODS
Tissue samples from 110 patients with GERD (n = 43), BE (n = 20), and BC (n = 47) were obtained in routine upper GI endoscopy. Expression levels of COX-2 were measured by quantitative real-time reverse trancriptase polymerase chain reaction (RT-PCR). Also, 24-h pH monitoring was performed in all patients of the GERD study group and the DeMeester composite score was used to match COX-2 mRNA expression with the severity of acid exposure in the lower esophagus.


RESULTS
COX-2 mRNA is progressively upregulated within the metaplasia-dysplasia-adenocarcinoma (MDA) sequence (p = 0.001). COX-2 levels of the squamous epithelium in the distal esophagus from patients with GERD and a pathologic mean DeMeester score (>14.72) were significantly higher than in patients with normal DeMeester scores (p = 0.01).


CONCLUSIONS
In summary our findings suggest that alterations in COX-2 mRNA expression occur independently of endoscopic or histologic signs of GERD in the acid-exposed squamous epithelium of the distal esophagus. However, this early COX-2 increase in GERD is further upregulated within the MDA sequence for yet unknown reasons.
Lurje
Georg
G
Department of Visceral and Vascular Surgery, University of Cologne, Cologne, Germany.
Vallbohmer
Daniel
D
Collet
Peter H
PH
Xi
Huan
H
Baldus
Stephan E
SE
Brabender
Jan
J
Metzger
Ralf
R
Heitmann
Michaela
M
Neiss
Susanne
S
Drebber
Ute
U
Holscher
Arnulf H
AH
Schneider
Paul M
PM
D000230:Adenocarcinoma / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D018450:Disease Progression; D004848:Epithelium / Q000473:pathology; D004938:Esophageal Neoplasms / Q000378:metabolism*; D005260:Female; D005764:Gastroesophageal Reflux / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D012333:RNA, Messenger; D051546:Cyclooxygenase 2