title: Nuclear accumulation of beta-catenin occurs commonly in the epithelial cells of juvenile polyps.
abstract: In the two conditions juvenile polyps (JPs) and juvenile polyposis coli (JPC), colonic polyps may have overlapping histologic and phenotypic appearance, but JPC confers a significant risk for colon adenocarcinoma. Although not thought to contain adenomatous polyposis coli (APC) mutations, the status of beta-catenin and full-length APC protein expression in JPs is not known. We evaluated beta-catenin and full-length APC protein expression in JPs from children with JPs and JPC. Cases were identified through endoscopic procedure records. Immunohistochemistry was performed for beta-catenin and full-length APC protein. Loss of heterozygosity at the APC gene locus on chromosome 5 was assessed using two APC-linked microsatellite markers. Polyp and normal colonic tissue were analyzed from 36 children with JPs and 9 with JPC. Both APC and beta-catenin immunoreactivity were present in epithelial cells from all samples but in different patterns. In all normal colon and polyp samples, APC expression was cytoplasmic with maximal immunoreactivity in the goblet cells. In contrast, beta-catenin immunoreactivity in epithelial cells was limited to the plasma membrane in normal colon but was both cytoplasmic and nuclear in all 45 JPs. No evidence of APC gene loss of heterozygosity was found. In polyps from children with JPs and JPC, nuclear beta-catenin accumulation is a consistent feature, and it is not due to APC gene mutation or loss of full-length APC protein expression. Thus, beta-catenin accumulation may be intrinsic to the formation of juvenile-type polyps through an as-yet-undefined mechanism.
authors.affiliation: Department Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA. Hoffenberg.Edward@tchden.org
authors.forename: Michiko
authors.initials: M
authors.lastname: Iwamoto
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Hoffenberg
authors.forename: John M
authors.initials: JM
authors.lastname: Carethers
authors.forename: Ryan
authors.initials: R
authors.lastname: Doctolero
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tajima
authors.forename: Kentaro
authors.initials: K
authors.lastname: Sugano
authors.forename: Wilbur A
authors.initials: WA
authors.lastname: Franklin
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Ahnen
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000096:biosynthesis; D000293:Adolescent; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D003111:Colonic Polyps / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D017491:Genes, APC; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D019656:Loss of Heterozygosity; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051176:beta Catenin
chemical_list: D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D051176:beta Catenin