Increased Cyclooxygenase-2 Expression in Juvenile Polyposis Syndrome

W. Arnout van Hattem, Lodewijk A.A. Brosens, Susan Y. Marks, Anya N.A. Milne, Susanne van Eeden, Christine A. Iacobuzio-Donahue, Ari Ristimäki, Francis M. Giardiello, G. Johan A. Offerhaus

Research output: Contribution to journalArticlepeer-review

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, 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 (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.

Original languageEnglish (US)
Pages (from-to)93-97
Number of pages5
JournalClinical Gastroenterology and Hepatology
Volume7
Issue number1
DOIs
StatePublished - Jan 2009

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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