title: Epithelial markers of colorectal carcinogenesis in ulcerative colitis and primary sclerosing cholangitis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Videnska 1958, 14021 Prague 4, Czech Republic. pawo@ikem.cz
authors.forename: Pavel
authors.initials: P
authors.lastname: Wohl
authors.forename: Tomas
authors.initials: T
authors.lastname: Hucl
authors.forename: Pavel
authors.initials: P
authors.lastname: Drastich
authors.forename: David
authors.initials: D
authors.lastname: Kamenar
authors.forename: Julius
authors.initials: J
authors.lastname: Spicak
authors.forename: Eva
authors.initials: E
authors.lastname: Honsova
authors.forename: Eva
authors.initials: E
authors.lastname: Sticova
authors.forename: Alena
authors.initials: A
authors.lastname: Lodererova
authors.forename: Jan
authors.initials: J
authors.lastname: Matous
authors.forename: Martin
authors.initials: M
authors.lastname: Hill
authors.forename: Petr
authors.initials: P
authors.lastname: Wohl
authors.forename: Milos
authors.initials: M
authors.lastname: Kucera
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D016022:Case-Control Studies; D015209:Cholangitis, Sclerosing / Q000209:etiology / Q000378:metabolism* / Q000601:surgery; D003093:Colitis, Ulcerative / Q000150:complications / Q000378:metabolism* / Q000601:surgery; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000209:etiology; D051546:Cyclooxygenase 2 / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Colorectal carcinoma; Cyclooxygenase-2; Imunohistochemistry; Liver transplantation; Primary sclerosing cholangitis; Ulcerative colitis; bcl2; p53