title: Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps.
abstract: Juvenile polyps are regarded as hamartomatous polyps and occur in sporadic and familial syndromic settings. There is increased risk of gastrointestinal neoplasia in patients with juvenile polyposis syndrome, but the molecular mechanisms are not known. We therefore studied 78 colorectal juvenile polyposis from 12 patients with juvenile polyps syndrome and 34 sporadic juvenile polyps for epithelial dysplasia and genetic changes associated with colorectal neoplasia. Dysplasia occurred in 31% of syndromic juvenile polyps but not in sporadic juvenile polyps (P < 0.0001). Topographic control of proliferation and expression of the cyclin-dependent kinase inhibitor p21(WAFI/CIP1) seen in native colorectal epithelium was lost in 79% of dysplastic juvenile polyps and in 8% of nondysplastic juvenile polyps (P < 0.000001). Somatic mutations in the adenomatous polyposis coli (APC) gene were demonstrated in 50% of dysplastic juvenile polyps (3 of 6) but not in any of 16 juvenile polyps without dysplasia (P = 0.01). Both sporadic and syndromic juvenile polyps had K-ras mutations (14%) and there was no relationship to dysplasia. p53 gene product overexpression identified by immunohistochemical staining occurred rarely in dysplastic juvenile polyps (2 of 24, 8%). Our results indicate that the multiple genetic alterations involved in usual colorectal neoplasia also play a role in neoplastic transformation of juvenile polyps, predominantly in juvenile polyposis syndrome.
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine and Hospital, Baltimore, Maryland, USA.
authors.forename: T T
authors.initials: TT
authors.lastname: Wu
authors.forename: B
authors.initials: B
authors.lastname: Rezai
authors.forename: A
authors.initials: A
authors.lastname: Rashid
authors.forename: M C
authors.initials: MC
authors.lastname: Luce
authors.forename: M C
authors.initials: MC
authors.lastname: Cayouette
authors.forename: C
authors.initials: C
authors.lastname: Kim
authors.forename: N
authors.initials: N
authors.lastname: Sani
authors.forename: L
authors.initials: L
authors.lastname: Mishra
authors.forename: C A
authors.initials: CA
authors.lastname: Moskaluk
authors.forename: J H
authors.initials: JH
authors.lastname: Yardley
authors.forename: S R
authors.initials: SR
authors.lastname: Hamilton
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics / Q000473:pathology*; D000293:Adolescent; D000328:Adult; D002467:Cell Nucleus / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003106:Colon / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004848:Epithelium / Q000473:pathology; D005260:Female; D017491:Genes, APC / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007417:Intestinal Polyps / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000235:genetics / Q000473:pathology*; D012007:Rectum / Q000473:pathology*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen