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, 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: 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
• Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Clin Gastroenterol Hepatol) Vol. 7 Issue 1 Pg. 93-7 (Jan 2009) ISSN: 1542-7714 [Electronic] United States
• PMID: 19124115 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Surface
• CCAAT-Enhancer-Binding Protein-beta
• ELAV Proteins
• ELAV-Like Protein 1
• ELAVL1 protein, human
• RNA-Binding Proteins
• Cyclooxygenase 2
• BMPR1A protein, human
• Bone Morphogenetic Protein Receptors, Type I

Topics

• Adenomatous Polyposis Coli (physiopathology)
• Adolescent
• Adult
• Antigens, Surface (biosynthesis)
• Bone Morphogenetic Protein Receptors, Type I (genetics)
• CCAAT-Enhancer-Binding Protein-beta (biosynthesis)
• Child
• Child, Preschool
• Cyclooxygenase 2 (biosynthesis)
• ELAV Proteins
• ELAV-Like Protein 1
• Gene Expression Profiling
• Humans
• Infant
• Middle Aged
• Oligonucleotide Array Sequence Analysis
• RNA-Binding Proteins (biosynthesis)