A high degree of aneuploidy, loss of p53 gene, and low soluble p53 protein serum levels are detected in ulcerative colitis patients.
OBJECTIVE
The causes for the increased risk of colorectal cancer associated with ulcerative colitis have not been fully defined. Colonic tissue of ulcerative colitis patients was examined for changes in chromosome-17-centromere copy number, loss of the p53 gene, and alterations in serum levels of the 53-kDa protein. This study was performed under the assumption that these molecular events correlate with ulcerative colitis status and duration.


METHODS
Ulcerative colitis patients (n = 42) and healthy controls (n = 37) participated in the study. All participants were histopathologically and medically diagnosed. The stage of ulcerative colitis patients was stratified according to increasing risk factors for the development of colorectal cancer: left-sided colitis, pancolitis, sclerosing cholangitis, and dysplasia-associated lesions or masses. Changes in centromere number of chromosome 17 alone or in association with changes in copy number of the p53 gene were analyzed in colon tissue biopsies by fluorescence in situ hybridization. Serum p53 level was determined in blood samples by immunoprecipitation followed by separation using high-pressure liquid chromatography.


RESULTS
Changes in chromosome 17 and p53 copy number and lower levels of serum p53 protein in ulcerative colitis patients directly correlated with colorectal cancer risk factors. All values significantly differed from controls. Significant direct correlations were obtained for ulcerative colitis disease duration, levels of p53 in the serum, and extent of aneuploidy.


CONCLUSIONS
We demonstrate that in the colonic mucosa of ulcerative colitis patients, high levels of genomic instability, changes in p53 gene copy number, and lower levels of p53 in the serum directly correlate with the extent of disease duration and increased risk factors for colorectal cancer. Any of the measurements described herein can provide an acceptable prognostic tool in the assessment of colorectal cancer risk in ulcerative colitis patients.
Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot, Israel.
Maya
M
Rosman-Urbach
Yaron
Y
Niv
Yehudith
Y
Birk
Patricia
P
Smirnoff
Igor
I
Zusman
Sara
S
Morgenstern
Betty
B
Schwartz
D000328:Adult; D000368:Aged; D000782:Aneuploidy; D001706:Biopsy; D016022:Case-Control Studies; D002886:Chromosomes, Human, Pair 17; D003093:Colitis, Ulcerative / Q000097:blood* / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics; D004171:Diploidy; D005260:Female; D016158:Genes, p53; D042822:Genomic Instability; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007413:Intestinal Mucosa / Q000473:pathology; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000097:blood*
D016159:Tumor Suppressor Protein p53