Background & Aims Gastrointestinal juvenile polyps may occur in juvenile polyposis

Background & Aims Gastrointestinal juvenile polyps may occur in juvenile polyposis syndrome (JPS) or sporadically. with sporadic juvenile polyps using tissue microarray analysis. Two additional markers Hu-antigen 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 (< .001). Also JPS patients with a germline defect experienced 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 (= .022) but not in sporadic juvenile polyps. Conclusions Juvenile polyposis and sporadic juvenile polyps show unique expression profiles of COX-2 that RU 58841 may have clinical implications. Juvenile polyps occur in about 1% of the pediatric populace and most often are sporadic solitary lesions of the RU 58841 colorectum. 1 These hamartomatous polyps are characterized by distorted and dilated crypts with reactive changes of the epithelium and an abundance of stroma. In contrast juvenile polyposis syndrome (JPS) is an autosomal-dominant condition characterized by multiple juvenile polyps throughout the gastrointestinal tract.2 In JPS juvenile polyps often contain relatively less stroma fewer dilated crypts and more epithelial proliferative activity than their sporadic counterparts.3 Sporadic juvenile polyps are not associated with an increased risk of gastrointestinal malignancy.4 However in juvenile polyposis a recently performed person-year analysis showed a relative risk for colorectal malignancy of 34% and a cumulative lifetime risk of 39%.5 Germline mutations in either or are found in 50% to 60% of JPS cases.6-9 The transforming growth factor-β co-receptor endoglin has been suggested as a predisposition gene for JPS although this is still under debate.9-11 mutation may possess a more aggressive gastrointestinal JPS phenotype with higher incidence of neoplastic switch compared with those with mutation. 13-15 But much remains unknown about the molecular-genetic phenotype of juvenile polyps. The increased risk of malignancy in JPS patients and the unique histologic appearance of JPS polyps suggest differences in molecular biology of JPS versus sporadic juvenile polyps. Cyclooxygenase-2 (COX-2) is usually a key enzyme in the conversion of arachidonic acid to prostaglandins and affects several transmission transduction pathways modulating inflammation and cell proliferation.16 17 COX-2 may play a crucial role in intestinal tumorigenesis through changes F2RL1 in cellular adhesion local invasion and inhibition of apoptosis and is up-regulated in consecutive stages of the colorectal adenoma-carcinoma sequence in patients with sporadic colorectal malignancy and in familial adenomatous polyposis.18-20 Hu-antigen R (HuR) and CCAAT/enhancer-binding protein β (C/EBP-β) interact with COX-2 and may be involved in regulation of COX-2 expression in juvenile polyps. HuR is an messenger RNA (mRNA)-binding protein capable of inhibiting quick mRNA degradation and is associated with COX-2 expression. 21 Nucleocytoplasmic translocation is necessary for HuR activation.22 C/EBP-β is a transcription factor regulating proliferation and differentiation 23 capable of inducing COX-2 expression. 24 Increased C/EBP-β correlates with invasiveness in human colorectal malignancy.25 In this study we RU 58841 compare COX-2 protein expression in polyps of a well-defined group of JPS patients with sporadic juvenile polyps using immunohistochemistry on tissue microarray. HuR and C/EBP-β expression were examined to investigate their relationship to COX-2 expression in RU 58841 JPS and sporadic juvenile polyps. Methods Tissue Selection Eighty-two patients diagnosed RU 58841 between 1985 and 2004 with one or more juvenile polyps were identified in a retrospective RU 58841 search in the Department of Pathology databases of The Johns Hopkins Hospital in Baltimore MD and the Academic Medical Centre in Amsterdam The Netherlands. The research was performed in accordance with the ethical guidelines of the research review committee of these institutions. Clinical and family history data were examined and polyps were histologically re-evaluated by an experienced pathologist (G.J.A.O.) to confirm the diagnosis of JPS or sporadic juvenile polyps. Also all JPS patients underwent thorough genetic analysis through direct sequencing and multiplex ligation-dependent probe amplification analysis.9.