A High Degree of Aneuploidy, Loss of p53 Gene, and Low Soluble p53 Protein Serum Levels Are Detected in Ulcerative Colitis Patients

Abstract

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.

Ulcerative colitis and cancer

“…Furthermore, percentage of patients with aneuploidy increases after duration of more than 10 years compared to patients with dysplasia findings that are found more often with disease duration of over 20 years [35]. Other studies confirmed that DNA aneuploidy is stable, widely spread (hence sampling error is minimal), may precede dysplasia (hence represents an early marker), and is evident 10 years after onset of colitis in young patients [23,25,55,63,68,75,76]. In addition to duration, aneuploidy correlates with extent of disease and is associated with total colitis [23,74].…”

“…Aneuploidy represents an early alteration during neoplastic transformation in UC [24,35,68,75]. Holzman et al [35] noted that aneuploidy is present in 8.7% of patients with UC and the frequency increased with increased duration of the disease (>10 years).…”

“…Mutation in the APC gene occurs less frequently in CC than SCRC but since UC follows the process of clonal expansion this genetically aberrant but pre-neoplastic clone is more widespread and can be more easily detectable than histological dysplasia [24]. Changes in p53 gene expression and lower serum levels of p53 protein are common, occur as early events, and correlate with extent of disease duration and increased risk for CRC [30,75,78]. Loss of p53 is present in 89% of patients exhibiting DALM, 71% of patients with PSC, 35% of patients with pancolitis, and 9% of patients with left colitis [75].…”

“…Changes in p53 gene expression and lower serum levels of p53 protein are common, occur as early events, and correlate with extent of disease duration and increased risk for CRC [30,75,78]. Loss of p53 is present in 89% of patients exhibiting DALM, 71% of patients with PSC, 35% of patients with pancolitis, and 9% of patients with left colitis [75]. The extent of LOH directly correlates with severity of neoplasia and gradually increases as UC stage becomes more prone to cancer development, as significant LOH occurs in 63% of patients with HGD and 33% with LGD [75,77].…”

“…Loss of p53 is present in 89% of patients exhibiting DALM, 71% of patients with PSC, 35% of patients with pancolitis, and 9% of patients with left colitis [75]. The extent of LOH directly correlates with severity of neoplasia and gradually increases as UC stage becomes more prone to cancer development, as significant LOH occurs in 63% of patients with HGD and 33% with LGD [75,77]. Allelic loss in the p53 gene is an early molecular event in dysplasia/carcinoma and may be connected to malignant change and mutations closely correlate with aneuploidy that precedes dysplasia [12,28,30,55].…”