Molecular alterations in chronic ulcerative colitis-associated and sporadic hyperplastic polyps: a comparative analysis.
OBJECTIVE
There is growing interest in the biological and molecular features and neoplastic potential of colonic hyperplastic polyps because of the recent finding of K-ras mutations in many of these lesions. Hyperplastic polyps may also develop in chronic ulcerative colitis (CUC), but it is unclear if these are biologically similar to the sporadic type. The aim of this study was to evaluate and compare the molecular profile of CUC-associated hyperplastic polyps with sporadic hyperplastic polyps of the colon.


METHODS
Thirty-nine hyperplastic polyps from 26 CUC patients, 39 sporadic hyperplastic polyps from 29 age- and sex-matched patients without CUC, and 26 colonic mucosal biopsies from 22 patients with CUC but without hyperplastic polyps were analyzed by polymerase chain reaction for loss of heterozygosity of APC, 3p, p53, and p16 and for mutations in codons 12, 13, and 61 of the K-ras gene. Immunohistochemical evaluations for the proliferation-associated nuclear peptide Ki67 (MIB-1) and p27 were also performed on a subset of hyperplastic polyps.


RESULTS
CUC-associated hyperplastic polyps showed a proportion of genetic alterations (47%) similar to that of sporadic hyperplastic polyps (33%) (p > 0.05), and neither significantly differed from chronically inflamed mucosae in CUC patients without hyperplastic polyps. Furthermore, in a small group of CUC patients in which informative tissue was available from both their hyperplastic polyps and adjacent flat colitic mucosae, the polyps contained mutations that were not present in the underlying mucosa. Loss of heterozygosity of APC, 3p, p53, p16, and K-ras mutations were present in 21%, 40%, 27%, 20%, and 19% of CUC patients with hyperplastic polyps, respectively, and in 0%, 11%, 20%, 13%, and 13% of non-CUC patients with sporadic polyps, respectively. Both CUC-associated and sporadic hyperplastic polyps showed a substantial number of cases (46% and 64% of cases, respectively) with loss of p27 expression, and both types of lesions showed similar MIB-1 proliferation indices.


CONCLUSIONS
These data suggest that CUC-associated hyperplastic polyps are genotypically similar to the sporadic type. This study adds to the expanding list of molecular alterations that have been discovered in hyperplastic polyps, and lends further support to the controversial theory that these lesions may have neoplastic potential.
Odze
Robert D
RD
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Brien
Tom
T
Brown
Charlotte A
CA
Hartman
Christopher J
CJ
Wellman
Axel
A
Fogt
Franz
F
D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003111:Colonic Polyps / Q000209:etiology* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D017491:Genes, APC; D019942:Genes, p16; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D005838:Genotype; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation