Systematic review: cyclo-oxygenase-2 in human oesophageal adenocarcinogenesis S. MEHTA*, A. BODDY*, I. T. JOHNSON  & M. RHODES* *Department of Upper Gastrointestinal Surgery, Norfolk and Norwich Univer- sity Hospital, Colney Lane, Norwich;  Institute of Food Research, Norwich Research Park, Colney, Norwich, UK Correspondence to: Dr S. Mehta, Flat 11 Magdalene Court, Gigant Street, Salisbury SP1 2DL, UK. E-mail: gree0123@hotmail.com Publication data Submitted 18 May 2006 First decision 20 June 2006 Resubmitted 12 July 2006 Resubmitted 16 July 2006 Accepted 24 July 2006 SUMMARY Background Published in vitro and animal in vivo studies have demonstrated that cyclo-oxygenase-2 plays an important role during oesophageal adeno- carcinogenesis. However, the extent to which these studies are directly relevant to events in the human lower oesophagus is questionable. Aim To perform a systematic review of all available human studies that have evaluated levels of cyclo-oxygenase-2 expression during the progres- sion from Barrett’s metaplasia to oesophageal adenocarcinoma. Methods A literature search was performed to identify all studies which qualita- tively or quantitatively assessed cyclo-oxygenase-2 protein or gene expression in either Barrett’s, dysplastic or adenocarcinoma tissue in humans. Results A total of 27 studies met the inclusion criteria. There was general agree- ment that cyclo-oxygenase-2 was either absent or very weakly expressed in normal oesophageal squamous mucosa, but considerable disagreement regarding the presence of cyclo-oxygenase-2 in Barrett’s and low-grade dysplasia. All studies agreed that high-grade dysplasia and adenocarcinoma expressed cyclo-oxygenase-2 to some extent although levels varied considerably between tissue samples. Conclusions There is conflicting evidence in the literature for cyclo-oxygenase-2 playing an important role in early oesophageal adenocarcinogenesis. Other non-cyclo-oxygenase-2 targets may account for the epidemiologi- cal data supporting the use of non-steroidal anti-inflammatory drugs in the chemoprevention of oesophageal adenocarcinoma. Aliment Pharmacol Ther 24, 1321–1331 Alimentary Pharmacology & Therapeutics ª 2006 The Authors 1321 Journal compilation ª 2006 Blackwell Publishing Ltd doi:10.1111/j.1365-2036.2006.03119.x