W1091 Increased Cyclooxygenase-2 Expression in Juvenile Polyposis Syndrome

Abstract

Background & Aims—Gastrointestinal juvenile polyps may occur in juvenile polyposis syndrome (JPS) or sporadically. JPS is an autosomal-dominant condition caused by a germline defect in SMAD4 or BMPR1A in 50% to 60% of cases, and is characterized by multiple juvenile polyps, predominantly in the colorectum. JPS has an increased risk of gastrointestinal malignancy but sporadic juvenile polyps do not. Cyclooxygenase-2 (COX-2) expression is increased in gastrointestinal tumorigenesis and familial adenomatous polyposis. Inhibition of COX-2 leads to regression of colorectal adenomas in familial adenomatous polyposis patients and inhibits gastrointestinal tumorigenesis. To investigate the role of COX-2 in juvenile polyps, we compared the expression of COX-2 in juvenile polyps from a well-defined group of juvenile polyposis patients and sporadic juvenile polyps. Methods—COX-2 expression was assessed in 24 genetically well-defined JPS patients and 26 patients with sporadic juvenile polyps using tissue microarray analysis. Two additional markers, Huantigen R, a stabilizer of messenger RNA, and CCAAT/enhancer-binding protein β, a transcription factor, both associated with increased COX-2 expression, also were investigated. Results—Increased COX-2 expression in JPS patients was noted compared with patients with sporadic juvenile polyps (P < .001). Also, JPS patients with a BMPR1A germline defect had higher COX-2 expression than did JPS patients in whom no germline mutation was detected. High COX-2 levels correlated with increased cytoplasmic Hu-antigen R expression in JPS polyps (P = .022), but not in sporadic juvenile polyps. Conclusions—Juvenile polyposis and sporadic juvenile polyps show distinctive expression profiles of COX-2 that may have clinical implications. Juvenile polyps occur in about 1% of the pediatric population and most often are sporadic, solitary lesions of the colorectum. 1 These hamartomatous polyps are characterized by distorted and dilated crypts with reactive changes of the epithelium and an abundance of stroma. In