Cyclo-oxygenase-2 expression in Barrett's oesophageal carcinogenesis: an immunohistochemical study

Background: The incidence of Barrett's oesophageal adenocarcinoma is increasing more rapidly than any other malignancy in industrialized countries. Cyclo-oxygenase-2 appears to play an important role in gastrointestinal carcinogenesis. Previous studies on cyclo-oxygenase-2 expression in Barrett's oesophageal carcinogenesis have utilized tissue samples obtained from different patients. We sought a definitive comparison of cyclo-oxygenase-2 expression in the sequence of Barrett's metaplasia-dysplasia-adenocarcinoma within the same patients. Methods: Paraffin-embedded oesophago-gastrectomy specimens from 20 patients, containing successive stages of Barrett's metaplasia, high-grade dysplasia and adenocarcinoma, were analysed for cyclo-oxygenase-2 expression by immunohistochemistry. Results: Cyclo-oxygenase-2 was constitutively expressed in the basal layers of cells in the adjacent normal squamous oesophageal epithelium, but a higher cyclo-oxygenase-2 expression was observed in Barrett's metaplasia. A further increase in cyclo-oxygenase-2 expression was detected in high-grade dysplasia, but cyclo-oxygenase-2 was decreased in adenocarcinoma tissue, regardless of its stage or level of differentiation. Conclusions: Cyclo-oxygenase-2 expression is progressively increased when squamous oesophageal epithelium develops into Barrett's metaplastic epithelium and then into high-grade dysplasia, but appears to decrease when adenocarcinoma develops. These findings may be significant for an effective chemo-prevention strategy with selective cyclo-oxygenase-2 inhibitors.