title: Increased cyclooxygenase-2 expression in juvenile polyposis syndrome.
abstract: OBJECTIVE
  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 beta, 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.
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands. W.A.vanHattem@umcutrecht.nl
authors.forename: W Arnout
authors.initials: WA
authors.lastname: van Hattem
authors.forename: Lodewijk A A
authors.initials: LA
authors.lastname: Brosens
authors.forename: Susan Y
authors.initials: SY
authors.lastname: Marks
authors.forename: Anya N A
authors.initials: AN
authors.lastname: Milne
authors.forename: Susanne
authors.initials: S
authors.lastname: van Eeden
authors.forename: Christine A
authors.initials: CA
authors.lastname: Iacobuzio-Donahue
authors.forename: Ari
authors.initials: A
authors.lastname: Ristimäki
authors.forename: Francis M
authors.initials: FM
authors.lastname: Giardiello
authors.forename: G Johan A
authors.initials: GJ
authors.lastname: Offerhaus
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000503:physiopathology*; D000293:Adolescent; D000328:Adult; D000954:Antigens, Surface / Q000096:biosynthesis; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D020869:Gene Expression Profiling; D006801:Humans; D007223:Infant; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016601:RNA-Binding Proteins / Q000096:biosynthesis
chemical_list: D000954:Antigens, Surface; D022782:CCAAT-Enhancer-Binding Protein-beta; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D016601:RNA-Binding Proteins; D051546:Cyclooxygenase 2; C498211:BMPR1A protein, human; D052005:Bone Morphogenetic Protein Receptors, Type I