Cyclooxygenase-2 expression in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence.
OBJECTIVE
Increased expression of the inducible cyclooxygenase 2 (COX-2) enzyme has been detected in esophageal and colonic adenocarcinoma, and intake of aspirin and non-steroidal anti-inflammatory drugs, known COX-2 inhibitors, have been associated with reduced tumor formation. Elevated COX-2 mRNA but variable protein expression has been demonstrated in Barrett's epithelium, and we have, therefore, sought to evaluate the expression of COX-2 protein throughout the Barrett's metaplasia-dysplasia-adenocarcinoma sequence.


METHODS
Paraffin-embedded esophageal biopsies from 56 different patients with Barrett's esophagus were analyzed for COX-2 expression by immunohistochemistry. Twenty contained nondysplastic intestinal and gastric metaplasia, 12 demonstrated low-grade dysplasia (LGD), 12 high-grade dysplasia (HGD), and 12 contained invasive adenocarcinoma.


RESULTS
Epithelial expression of COX-2 protein was detected in 75% (15/20) of benign cases, 83% (10/12) of cases with LGD, and 100% of cases with HGD or adenocarcinoma. Using a semiquantitative analysis, median staining scores for the groups were 2, 3, 14, and 13, respectively (scale 0-16), with the expression being significantly higher in the HGD and cancer groups compared to benign and LGD groups (p < 0.001).


CONCLUSIONS
This study demonstrates clear COX-2 expression in the epithelial cells in Barrett's metaplasia, confirms elevated expression in adenocarcinoma, and shows that the elevation in expression occurs in the progression from LGD to HGD.
Morris
C D
CD
Department of Surgery, Hope Hospital, Manchester, United Kingdom.
Armstrong
G R
GR
Bigley
G
G
Green
H
H
Attwood
S E
SE
D000230:Adenocarcinoma / Q000201:enzymology* / Q000209:etiology*; D001471:Barrett Esophagus / Q000201:enzymology* / Q000473:pathology*; D051546:Cyclooxygenase 2; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000209:etiology*; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis*; D008565:Membrane Proteins; D008679:Metaplasia / Q000201:enzymology; D010544:Peroxidases / Q000096:biosynthesis*; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012189:Retrospective Studies
D007527:Isoenzymes; D008565:Membrane Proteins; D010544:Peroxidases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases