Epithelial markers of colorectal carcinogenesis in ulcerative colitis and primary sclerosing cholangitis

Abstract

Aim: To evaluate the expression of epithelial markers of colorectal carcinogenesis in patients with long-term ulcerative colitis (UC) and primary sclerosing cholangitis (PSC) before and after transplantation.

Methods: Eight patients with UC and PSC prior to liver transplantation (PSC-UC), 22 patients with UC after liver transplantation for PSC (OLT), 9 patients with active ulcerative colitis without PSC (UCA), 7 patients with UC in remission (UCR) and 10 controls (N) underwent colonoscopy with multiple biopsies. Specimens were analysed histologically and semi-quantitatively immunohistochemically for p53, Bcl-2 and cyclooxygenase-2 (COX-2) markers. Statistical analysis was performed by Kruskal-Wallis and Fisher's exact tests.

Results: PSC-UC had a statistically significantly higher expression of p53 in the nondysplastic mucosa as compared to OLT, UCA, UCR and N (P < 0.05). We also found a statistically significant positive correlation between the incidence of PSC and the expression of p53 (P < 0.001). UCA had a higher p53 expression as compared to UCR. OLT had a significantly lower expression of p53 as compared with PSC-UC (P < 0.001). Bcl-2 had a significant higher bcl-2 expression as compared with controls. No difference in COX-2 expression between PSC-UC, UCR and UCA was found. UCA had higher COX-2 expression as compared to UCR. We also found a statistically significant positive correlation between the expression of COX-2 and p53. Patients after liver transplantation for PSC had a statistically significantly lower expression of the p53 compared with PSC-UC (P < 0.001). PSC-UC had the same inflammatory endoscopic activity as OLT and UCR when evaluated with the Mayo score.

Conclusion: Our study shows that the nondysplatic mucosa of UC patients with PSC is characterised by a higher expression of the tumour suppressor gene p53, suggesting a higher susceptibility of cancer. This p53 overexpression correlates with the presence of PSC whilst it is not present in patients with UC after liver transplantation for PSC.

Keywords: Colorectal carcinoma; Cyclooxygenase-2; Imunohistochemistry; Liver transplantation; Primary sclerosing cholangitis; Ulcerative colitis; bcl2; p53.

Figure 1

Comparison of findings in percent (%) in all tested group. A: Comparison of intranuclear p53 gene expression in percent (%) in all tested group; B: Comparison of bcl-2 expression in percent (%) in all tested group; C: Comparison of COX-2 expression by immunohistochemistry in percent (%) in all tested group; D: Comparison of inflammatory disease activity by histology (0 = nonactive, 1 = mild, 2 = moderate, 3 = severe) in all tested group; E: Comparison of endoscopic findings by Mayo score in all tested group in all tested group. The bars with error bars represent group means with SEM. Differences between groups were evaluated using Dunn’s multiple comparisons with Bonferroni correction. ^aP < 0.05, ^bP < 0.01 vs N group; ^cP < 0.05, ^dP < 0.01 vs PSC-UC group; ^eP < 0.05, ^fP < 0.01 vs UCA group. UC: Ulcerative colitis; UCR: UC in remission; PSC: Primary sclerosing cholangitis; OLT: UC after liver transplantation for PSC; UCA: UC active disease; COX-2: Cyclooxygenase-2.