Expression Of COX-2 In Barrett's Esophagus And Esophageal Adenocarcinoma

Background:The incidence of esophageal adenocarcinoma (EAC) has increased rapidly, and is now the fastest increasing in all cancers. The prognosis of EAC is depressing with 5-yr survival of less than 10%. 80 percent of esophageal adenocarcinomas originate from Barrett's esophagus (BE), which is defined as the replacement of the normal squamous esophageal epithelium with specialized columnar lining. This condition is highly premalignant lesion for esophageal adenocarcinoma.Some epidemiological studies have indicated that nonsteroidal anti-inflammatory drugs (NSAIDs) could reduce the risk of colorectal cancer, prevent the development of esophageal adenocarcinoma in Barrett's esophagus. One possibility is that NSAIDs inhibit expression of COX-2. Cyclooxygenase (COX) is the rate-limiting enzyme for the high output production of prostaglandins from arachidonic acid. Two isoforms of the enzyme have been identifiedæ¡ŸOX-1 and COX-2. Recently, the importance of COX-2 in gastrointestinal carcinogenesis has been recognized. Many findings support the hypothesis that COX-2 is involved early in Barrett's-associated neoplastic progression. It has been thought that one contribution of COX-2 to carcinogenesis was related to its abilities to increase production of prostaglandins.Objective:To study the significance of cyclooxygenase-2 (COX-2) expression and PGE2 level in human BE and EAC.Methods:Using RT-PCR, immunohistochemistry and RIA, the expression of COX-2 mRNA, the distribution of COX-2 and the content of PGE2 were investigated in endoscopic biopsies of 16 BE -. 17 EAC and 20 control.Results:COX-2 mRNA was positive in 87.50% of BE, in 88.24% of EAC, while in 25% of control (P<0.01). No significant difference of COX-2 mRNA was found between BE and EAC(P > 0.1). Further more, COX-2 protein with Lmmunohistochemical staining was positive in the cytoplasm of Barrett epithelium (81.25%) and EAC (76.47%), compared with control (20.00%). No significant difference of COX-2 expression was found between BE and EAC(P>0.05). PGE2 levels (pg/mg) in BE (541.41 ?4.30) and EAC (559.22 ?7.77) were significantly higher than control (357.10 ?7.58) (PO.05). No significant difference of PGE2 levels was found between BE and EAC(P>0.05).Conclusions:1. COX-2 and its mRNA were overexpression in BE and EAC.2. PGE2 levels were increased in BE and EAC.3. COX-2 and PGE2 may be involved in development of Barrett's esophagus and esophageal adenocarcinoma.