Cyclooxygenase 2 expression in Barrett's esophagus and adenocarcinoma: Ex vivo induction by bile salts and acid exposure.
OBJECTIVE
Barrett's esophagus (BE) results from chronic, severe gastroesophageal reflux and predisposes to esophageal adenocarcinoma. Cyclooxygenase (COX)-2 is involved in chronic inflammation and epithelial cell growth. We investigated COX-2 expression in BE and esophageal adenocarcinoma to explore a potential relation between COX-2 expression and metaplasia or carcinogenesis.


METHODS
Endoscopic mucosal biopsy specimens of Barrett's intestinal metaplasia (n = 30), Barrett's dysplasia (n = 11), and esophageal adenocarcinoma (n = 5) were compared with normal esophagus (n = 46) and duodenum (n = 46) and analyzed by Western blotting and immunohistochemistry.


RESULTS
Immunoblots revealed constitutive expression of COX-2 in normal esophagus and duodenum. COX-2 protein expression was significantly higher in patients with Barrett's metaplasia, dysplasia, and adenocarcinoma compared with normal squamous esophageal or columnar duodenal epithelia and was heterogenous in different regions of the BE surface. Immunohistochemistry revealed prominent staining in the glands of BE, dysplasia, and adenocarcinoma and faint staining in the basal layers of squamous esophagus and the surface of the duodenum. In response to pulses of acid or bile salts in an ex vivo organ culture system, COX-2 expression increased significantly in BE tissues, and this effect was attenuated by the selective COX-2 inhibitor NS-398.


CONCLUSIONS
The results show COX-2 expression in normal esophagus, which increases significantly in BE and esophageal adenocarcinoma. COX-2 is regulated ex vivo by exposure to acid or bile salts.
Shirvani
V N
VN
Gastroenterology Section, Palo Alto Veterans Affairs Health Care System, Palo Alto, California 94304, USA.
Ouatu-Lascar
R
R
Kaur
B S
BS
Omary
M B
MB
Triadafilopoulos
G
G
D000143:Acids / Q000494:pharmacology; D000230:Adenocarcinoma / Q000201:enzymology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000201:enzymology*; D001647:Bile Acids and Salts / Q000494:pharmacology; D051546:Cyclooxygenase 2; D004386:Duodenum / Q000201:enzymology / Q000473:pathology; D004790:Enzyme Induction; D004938:Esophageal Neoplasms / Q000201:enzymology*; D004947:Esophagus / Q000201:enzymology / Q000473:pathology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008679:Metaplasia / Q000201:enzymology; D008875:Middle Aged; D009092:Mucous Membrane / Q000201:enzymology; D009924:Organ Culture Techniques; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012016:Reference Values
D000143:Acids; D001647:Bile Acids and Salts; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases