Increased cyclooxygenase-2 expression in juvenile polyposis syndrome.
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.
van Hattem
W Arnout
WA
Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands. W.A.vanHattem@umcutrecht.nl
Brosens
Lodewijk A A
LA
Marks
Susan Y
SY
Milne
Anya N A
AN
van Eeden
Susanne
S
Iacobuzio-Donahue
Christine A
CA
Ristimäki
Ari
A
Giardiello
Francis M
FM
Offerhaus
G Johan A
GJ
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
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