Cydooxygenase-2 in Barrett's Esophagus, Barrett's Adenocarcinomas, and Esophageal SCC: Ready for Clinical Trials

Lord, Reginald V. N.; Danenberg, Kathleen D.; Danenberg, Peter V.; Johnson, David
August 1999
American Journal of Gastroenterology;Aug1999, Vol. 94 Issue 8, p2313
Academic Journal
These studies investigated the role of cyclooxygenase gene expression in esophageal diseases. The study from Germany by Zimmerman et al. detected cytoplasmic cyclooxygenase- 2 (COX-2) protein expression by immunohistochemistry in 156 of 172 (91%) esophageal squamous cell carcinomas (SCC) and in 21 of 27 (78%) Barrett's-associated esophageal adenocarcinomas. There was a wide range in COX-2 immunoreactivity in different cancer specimens, and also within individual specimens. Western blot analysis of COX-2 protein levels was performed for some of the SCC samples, confirming the immunohistochemistry results. No COX-2 protein expression was detected immunohistochemically in Barrett's intestinal metaplasia tissues. There were no significant associations between COX immunoreactivity and tumor stage for either cancer type, except for a higher frequency of local lymph node metastases in SCC patients with low COX-2 expression. In vitro studies using SCC cell lines showed that expression of COX-2 at the mRNA level was associated with production of both COX-2 protein and high prostaglandin (PGE2 and 6-keto-PGFlα) levels. Finally, this study showed that treatment of the COX-2-expressing SCC cells with the COX inhibitors flusolide and NS-398 inhibited prostaglandin synthesis, suppressed proliferative and mitotic activity, and induced widespread apoptosis (the apoptotic effect was assessed with flusolide only). In the non-COX- 2-expressing cell line, none of these effects were observed. The earlier publication, by Wilson et al., from the University of Maryland School of Medicine, used a reverse transcriptase-polymerase chain reaction method to detect elevated COX-2 mRNA levels in 15 of 19 (79%) Barrett's intestinal metaplasia specimens, 2 of 2 (100%) Barrett's dysplasia specimens, and 5 of 5 (100%) Barrett's-associated adenocarcinomas. Increased levels of COX-2 protein, inducible nitric oxide synthase mRNA, and transforming growth factor-α mRNA were also present in similar proportions in Barrett's esophagus and adenocarcinoma tissues.


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