Significance of Cox2 Inhibitor for Esophageal Cancer From the Clinical and Experimental Estimate

Background Overall survival rate of esophageal cancer ranges from 5% to 10%. The development of preventive and novel treatment strategies is essential. We report experimental and clinical evidence that COX2 represent a potential molecular target for the treatment and prevention of esophageal cancer. Methods (A) Experiment:Thirty 8-week male wistar rats were exposed to duodenal content esophageal reflux. All animal underwent an esophagoduodenal anastomosis (EDA) with total gastrectomy in order to produce chronic esophagitis. In ten rats the sham (Control). They were sacrified at 40th week. Their esophagi were examined for HE,COX2,PGE2, PCNA and total bile acids in the esophageal lumen was measured. (B) Clinical: The expression of COX2 was examined for 68 specimens of esophageal squamous cell carcinoma(SCC) and the correlation of COX2 expression with clinicopatholigic features was examined. Results (A)EDA showed dysplasia, SCC and ADC. Total bile acid in the esophageal lumen was significantly increased in the EDA compared with the sham. PCNA LI and esophageal PGE2 were higher in dysplastic and cancer tissue than that of control. Overexpression of COX2 was shown in dysplastic and cancer tissue.(B) COX2 immunoreactivity was weak in 27(40%) and strong in 41(60%) of the carcinomas. The depth of tumors (p = 0.004),lymph node metastasis (p = 0.0009) and the stage of the tumors (p = 0.001) were progressively in ECCS with (strong). Survival was significantly reduced (p = 0.02) among patients with (strong) compared to (weak). Conclusion In this experimental study, we demonstrate that bile reflux of duodenal contents induce COX2 and increase prostaglandin synthesis in dysplastic and cancer tissue. Our study suggests that COX2 may play a role in esophageal carcinoma development and progression,COX2 inhibitors may be potential targets for the prevention or treatment of esophageal carcinoma.