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

doi:10.3748/wjg.v19.i14.2234

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Apr 14, 2013; 19(14): 2234-2241
Published online Apr 14, 2013. doi: 10.3748/wjg.v19.i14.2234

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

Pavel Wohl, Tomas Hucl, Pavel Drastich, David Kamenar, Julius Spicak, Eva Honsova, Eva Sticova, Alena Lodererova, Jan Matous, Martin Hill, Petr Wohl, Milos Kucera

Pavel Wohl, Tomas Hucl, Pavel Drastich, David Kamenar, Julius Spicak, Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Videnska 1958, 14021 Prague 4, Czech Republic

Eva Honsova, Eva Sticova, Alena Lodererova, Department of Pathology, Institute for Clinical and Experimental Medicine (IKEM), Videnska 1958, 14021 Prague 4, Czech Republic

Jan Matous, 2^nd Department of Internal Medicine, Third Faculty of Medicine, Charles University, 11640 Prague 1, Czech Republic

Martin Hill, Department of Biostatistics, Institute of Endocrinology, Charles University, 11640 Prague 1, Czech Republic

Petr Wohl, Milos Kucera, Institute for Clinical and Experimental Medicine (IKEM), Videnska 1958, 14021 Prague 4, Czech Republic

Author contributions: Wohl P, Honsova E, Sticova E and Lodererova A performed the majority of experiments and wrote the manuscript as main author; Spicak J, Kucera M, Drastich P, Hucl T and Kamenar D co-ordinated and provided the collection of all the human material; Wohl P and Matous J contributed the study and wrote the manuscript; Hill M performed biostatistics.

Supported by IGA Ministry of Health, Czech Republic, No. 7878/3

Correspondence to: Pavel Wohl, MD, Department of Hepatogastroenterology, Institute for Clinical and Experimental Medicine, Videnska 1958, 14021 Prague 4, Czech Republic. pawo@ikem.cz

Telephone: +420-26136-2139 Fax: +420-26136-2697

Received: November 7, 2012
Revised: January 9, 2013
Accepted: February 2, 2013
Published online: April 14, 2013

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