Die ansteigende Cyclooxygenase-2 Expression in der Metaplasie-Dysplasie-Karzinom Sequenz beim Barrett-Karzinom ist nicht assoziiert mit der inflammatorischen Umgebungsreaktion

Abstract

Background: Epidemiological data assume a reduction of risk for developing an adenocarcinoma of the esophagus for individuals taking NSAIDs. One of the inhibited enzymes, cyclooxygenase-2, is supposed to be of major influence in the pathogenesis of Barrett’s cancer. We examined a possible association between COX-2 protein expression and the progressive severity within Barrett’s metaplasia-dysplasia-carcinoma sequence and the type and extent of the corresponding inflammatory reaction. Methods: COX-2 protein expression was examined in precurser lesions (metaplasia, low-grade-and high-grade-dysplasia) as well as tumor tissue of 49 resection specimens. Thereby interindividual variability was minimized. Immunohistochemical staining was graded on a scale 0–3 based on the percentage of specific tumor cell staining. Active and chronic inflammatory reaction was scored on a scale 0–3 as defined by the Updated Sydney Classification. Results: COX-2 expression is significant lower in squamous epithelium than in Barrett’s metaplasia (p < 0.001). Within Barrett’s metaplasia-dysplasia-carcinoma sequence a significant progressive increase in protein expression was noticed (Friedman test: p < 0.0001). Individual statistical testing detected the most significant differences between squamous epithelium and Barrett’s metaplasia (Wilcoxon test: p < 0.001) as well as between low-grade and high-grade dysplasia (Wilcoxon test: p < 0.0001). No association was present between COX-2 expression and pT-categories or grading of the tumor. Active and chronic inflammation were significantly different between squamous epithelium and Barrett’s metaplasia (Wilcoxon test: p < 0.0001) but not between Barrett’s metaplasia and carcinoma. Conclusions: There is a significant association between COX-2 protein expression and progression of the Barrett’s metaplasia-dysplasia-carcinoma sequence not explicable through changes in kind or intensity of the inflammatory reaction of the environment. Therefore, selective COX-2 inhibitors might be used as chemoprevention strategy independently of the inflammatory reaction.