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P196. p53, COX‑2 and BCL‑2 in patients with ulcerative colitis with or without coexistence of the primary sclerosing cholangitis and after liver transplantation – immunohistochemical study

P. Wohl1,2, E. Honsova3, P. Drastich1, D. Kamenar1, J. Matous4, J. Spicak1

1IKEM, Hepato­gastroenterology, Prague, Czech Republic; 2IKEM, Prague, Czech Republic; 3IKEM, Pathology, Prague, Czech Republic; 43, Medical Faculty Charles University, 2nd Department of Internal Medicine, Prague, Czech Republic

Background: Ulcerative colitis (UC) is inflammatory bowel disease connected with higher occurrence of colorectal carcinoma. The risk is even higher in patients with UC and primary sclerosing cholangitis (PSC) and liver transplantation as well. The aim of this study is to evaluate epithelial markers expression of colorectal carcinogenesis in patients with long-term UC with or without PSC and after liver transplantation for PSC.

Methods: Included were 22 patients with UC after liver transplantation for PSC(OLT), 8 patients with UC-PSC without liver transplantation, 9 patients with active UC (UCA), 7 patients with UC in remission (UCR) and 10 controls (N). Specimens were analyzed histologically and semi-quantitatively imunohistochemically. For antigen detection we used two-level indirect imunoperoxidase reaction of BCL‑2 Oncoprotein, p53 (DakoCytomation), COX‑2 (Cayman). For the systemic detection we used imunoperoxidase polymer: Histofine Simple Stain MAX PO (Nichirei) and chromogen 3, 3' diaminobenzidin (DakoCytomation).

Results: UC-PSC had statistically significantly higher expression of p53 in the nondysplatic mucosae as compared to OLT, UCA, UCR and controls (p < 0.01). We also found a statistically significant positive correlation between the incidence of PSC and the expression of P53 (r = 0.4954, p < 0.01). The expression of COX‑2 group did not differ UCPSC and UCR, but the expression was higher in active colitis (p < 0.01). The expression of bcl‑2 was no difference in all groups. Transplant group had significantly lower expression of p53 versus nontransplant group (USPCS) (p < 0.01).

Conclusions: Our work shows that UC-PSC is associated with higher expression of tumor suppressor gene p53 in nondysplatic mucosae, and this confirms the increased neoplastic potential UC-PSC. PSC correlates with the amount of p53 expression. A surprising finding was that a group of UC after liver transplantation for PSC showed low expression of p53 in nondysplatic mucosae as compared to UC-PSC and this implies the hypothesis that liver transplantation is unknown mechanism associated with a statistically significant decrease in expression of p53 in the intestinal mucosa.