Document Detail


Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps.
MedLine Citation:
PMID:  9060832     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
T T Wu; B Rezai; A Rashid; M C Luce; M C Cayouette; C Kim; N Sani; L Mishra; C A Moskaluk; J H Yardley; S R Hamilton
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of pathology     Volume:  150     ISSN:  0002-9440     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  1997 Mar 
Date Detail:
Created Date:  1997-04-07     Completed Date:  1997-04-07     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  939-47     Citation Subset:  AIM; IM    
Affiliation:
Department of Pathology, Johns Hopkins University School of Medicine and Hospital, Baltimore, Maryland, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenomatous Polyposis Coli / genetics,  pathology*
Adolescent
Adult
Cell Nucleus / pathology
Child
Child, Preschool
Colon / pathology*
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / genetics
Epithelium / pathology
Female
Genes, APC / genetics
Genes, p53 / genetics
Genes, ras / genetics
Humans
Immunohistochemistry
Intestinal Polyps / chemistry,  genetics,  pathology*
Ki-67 Antigen / analysis
Male
Middle Aged
Precancerous Conditions / genetics,  pathology*
Rectum / pathology*
Grant Support
ID/Acronym/Agency:
CA47527/CA/NCI NIH HHS; CA62924/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Ki-67 Antigen
Comments/Corrections

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