Immunohistochemical Expression of P53and Oncogenes in Ulcerative Colitis-associated ColorectalCarcinoma

The role of the tumor suppressor gene p53and proto-oncogenes mdm-2, waf-1,and bcl-2 in sporadic colorectal carcinoma (CRC) hasbeen well investigated. However, little is known about the role ofthese genes in the development of ulcerative colitis-associatedcolorectal carcinoma (CAC). Colectomy specimens from patients with CAC,patients with ulcerative colitis (UC) and dysplasia, patients withlong-standing UC without carcinoma or dysplasia, and patients with CRC were investigated in comparison to normal colon (NC) specimens frompatients with diverticulosis without histologic signs of inflammation.Immunohistochemistry was performed with antibodies against p53, mdm-2,waf-1, and bcl-2; and staining was evaluated semiquantitatively with anexpression of more than 20% of tumor cell nuclei or epithelial cellnuclei in nontumor specimens considered "positive." Statisticalanalysis was performed using Fisher’s exact test. In carcinomas, p53 was positive in 50% of CRC tissues and 60% of CACtissues without statistical difference. Positive expression of p53 was found in most high-grade dysplasia but not inlow-grade dysplasia (p < 0.01). Whereas mdm-2 and bcl-2 were only sporadicallyexpressed, waf-1 was observed in most specimens, with ahigh prevalence in UC without carcinoma or dysplasia (11/15). NCspecimens were always negative for all antibodies. Immunohistochemicalexpression of p53, mdm-2, waf-1, and bcl-2 issimilar for CAC and CRC. The malignant potential of dysplasia in UC ispartially confirmed by a high prevalence of p53 and waf-1 expression, suggesting that CAC may develop alongpathways that are different from CRC. High expression ofwaf-1 in nonmalignant long-standing UC has to be provedover a long-term course in its role as an independent cancer riskfactor in UC patients.