Z Gastroenterol 2008; 46 - A68
DOI: 10.1055/s-2008-1079672

K-ras, Cox-2 and membrane β-catenin overexpression may be a marker of inflammatory bowel disease-associated intestinal cancer

T Molnár 1, Z Szepes 1, I Németh 2, P Szilágyi 3, F Nagy 1, L Tiszlavicz 2, T Wittmann 1
  • 11st Department of Internal Medicine, University of Szeged, Szeged, Hungary
  • 2Department of Pathology, University of Szeged, Szeged, Hungary
  • 3Department of Pathology, St. Margit Hospital, Budapest, Hungary

It has been known since 1928 that patients with ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC). Regular colonoscopic surveillance with multiple colonic biopsies is the mainstay of CRC prevention in UC, although it has not been proven to reduce mortality because of CRC and the number of biopsies necessary are questionable. Our aim was to determine the protein expression profile of UC associated CRC in the tumor and tumor-free tissue in comparison with mucosal biopsies from UC patients with long-lasting disease in order to find markers which suggest a high risk for CRC. Methods. Resected bowel of 19 patients with UC-associated intestinal cancer (male/female 8/11; mean age 56.2, range 26–79 years; T stage: 2 in 2, 3 in 12 and 4 in 5 patients) from different Hungarian tertier centers and multiple biopsies of 10 UC patients with pancolitis (male/female 4/6; mean age: 54, range 45–71, mean course of disease: 23.7 years) were investigated retrospectively by tissue microarray analysis. The protein expression profile of MLH1, MSH2, membrane β-catenin, PTEN, APC, K-ras, Cox-2, NOS, NFκB and VEGF were investigated. Results. The expression profile of p53, APC, K-ras, Cox-2 and membrane β-catenin were significantly different in the three groups. Each marker was significantly overexpressed in the tumorous and tumor-free tissue except for APC and p53, which showed overexpression in the tumor only. There was a highly significant difference in K-ras, Cox-2 and membrane β-catenin overexpression between tumor-free tissue of UC associated CRC and the samples of patients without CRC (p<0.0001). Conclusion. K-ras, Cox-2 and membrane β-catenin overexpression in the mucosa of patients with long-lasting UC may be a marker for progression to carcinoma throughout the colon. Therefore, a prospective study is necessary to prove whether the protein expression profile of biopsies from the distal part of the colon is enough to determine the carcinoma risk-profile of patients with UC.