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P133. K-ras, Cox-2 and membrane β-catenin positivity are characteristics of tumor-free mucosa in patients with ulcerative colitis-associated colorectal cancer

B. Tam1, Z. Szepes2, I. Németh3, F. Nagy2, L. Tiszlavicz2, T. Wittmann2, T. Molnar2

1Tolna County Teaching Hospital, Szekszard, Hungary; 2First Department of Medicine, University of Szeged, Szeged, Hungary; 3Institute of Pathology, University of Szeged, Szeged, Hungary

Introduction: Patients with inflammatory bowel disease (IBD) [ulcerative colitis (UC) and Crohn's disease (CD)] are at increased risk of developing gastrointestinal, mainly colorectal cancer (CRC). The main risk factors for malignancy are longstanding disease, extensive colitis, chronic colonic stenosis, primary sclerosing cholangitis and the family history of CRC. Random colonic biopsies can not completely prevent carcinoma formation in all patients.

Our aim was to identify immunohistological markers which may be used for routine CRC screening in UC patients.

Patients and Methods: The association between clinical characteristics and molecular pathogenetic alterations of IBD-associated intestinal carcinoma were examined retrospectively in a cohort of patients with IBD from a well-defined East Hungarian geographical area. We compared the immunohistological features of the malignant and the tumor-free tissue of the surgically removed large bowel in 20 UC patients with CRC (extension: 17 pancolitis, 3 left-sided colitis; male/female ration: 9/11; average age at the diagnosis of CRC: 56.2 [26–79] years; age at the diagnosis of UC 34.1 [11–61] years; disease duration: 23.7 [12–48] years) and 25 UC patients without CRC (mean disease duration: 23.7 years; extension: 21 pancolitis, 4 left-sided colitis). The following parameters were investigated by tissue microarray technique: grade of differentiation, lymphovascular invasion, perineural spreading, peritumoral inflammation, necrosis, desmoplastic reaction and the semiquantitative grade of the protein expression profile of p53, MLH1, MSH2, β-catenin, PTEN, APC, K-ras, Cox-2, NOS, NFκB and VEGF.

Results: Significant overexpressions of p53, APC, K-ras, Cox-2, membrane β-catenin, APC and p53 were observed in the malignant tissue. The APC and p53 positivity were exclusively characteristics for CRC, however, highly significant (p < 0.0001) overexpression of K-ras, Cox-2 and membrane β-catenin was detected in the tumor-free tissue.

Conclusion: Our results suggest that the presence of overexpressed K-ras, Cox-2 and membrane β-catenin protein in the entire colon might be associated with tumor formation in UC, and therefore they can be used as a reliable tool for CRC screening in UC patients with longstanding disease.