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

OBJECTIVE: Increased expression of the inducible cyclooxygenase 2 (COX-2) e nzyme has been detected in esophageal and colonic adenocarcinoma, and intak e of aspirin and nonsteroidal anti-inflammatory drugs, known COX-2 inhibito rs, have been associated with reduced tumor formation. Elevated COX-2 mRNA but variable protein expression has been demonstrated in Barrett's epitheli um, and we have, therefore, sought to evaluate the expression of COX-2 prot ein throughout the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. METHODS: Paraffin-embedded esophageal biopsies from 56 different patients w ith Barrett's esophagus were analyzed for COX-2 expression by immunohistoch emistry. Twenty contained nondysplastic intestinal and gastric metaplasia, 12 demonstrated low-grade dysplasia (LGD), 12 high-grade dysplasia (HGD), a nd 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 scor es for the groups were 2, 3, 14, and 13, respectively (scale 0-16), with th e expression being significantly higher in the HGD and cancer groups compar ed to benign and LGD groups (p < 0.001). CONCLUSIONS: This study demonstrates clear COX-2 expression in the epitheli al cells in Barrett's metaplasia, confirms elevated expression in adenocarc inoma, and shows that the elevation in expression occurs in the progression from LGD to HGD. (Am J Gastroenterol 2001;96:990-996. (C) 2001 by Am. Coll . of Gastroenterology).