Cyclooxygenase-2 expression in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence

Am J Gastroenterol. 2001 Apr;96(4):990-6. doi: 10.1111/j.1572-0241.2001.03599.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / etiology*
  • Barrett Esophagus / enzymology*
  • Barrett Esophagus / pathology*
  • Cyclooxygenase 2
  • Disease Progression
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / etiology*
  • Humans
  • Isoenzymes / biosynthesis*
  • Membrane Proteins
  • Metaplasia / enzymology
  • Peroxidases / biosynthesis*
  • Precancerous Conditions / enzymology*
  • Precancerous Conditions / pathology*
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Retrospective Studies


  • Isoenzymes
  • Membrane Proteins
  • Peroxidases
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases