Increased expression of proliferative Ki-67 nuclear antigen is correlated with dysplastic colorectal epithelium in ulcerative colitis

Because patients with ulcerative colitis have an increased long-term risk o f colorectal cancer, colonoscopic surveillance with multiple biopsies is co mmonly performed for histopathological detection of dysplasia to select hig h-risk patients for prophylactic colectomy. Improved differentiation betwee n neoplastic vs. nonneoplastic changes is needed because active inflammatio n may cause significant misinterpretation of nonneoplastic reactive/regener ative changes in the epithelium. We investigated whether the expression of proliferative antigens is correlated with various degrees of epithelial dys plasia and inflammatory changes in biopsy specimens from patients with long -standing ulcerative colitis. Colorectal biopsy specimens from patients und ergoing colonoscopic surveillance were analyzed immunohistochemically using two types of monoclonal antibodies: MIB-1 against Ki-67 and NCL-PCNA again st proliferating cell nuclear antigen for structural, active inflammatory, and dysplastic changes. Specimens from patients without inflammatory bowel disease or neoplasia were used as controls; these showed no increased proli feration. However, increased staining with the MIB-1 monoclonal antibody wa s detected in 9% of the specimens from patients with long-standing ulcerati ve colitis without active inflammation or dysplasia; this was significantly more common in specimens indefinite for dysplasia, probably positive (24%) , and in those with definite dysplasia of low (47%) or high grade (67%; P = 0.008). For increased PCNA staining, there was a non-significant correlati on (P = 0.30) with increasing degrees of dysplasia. Increased MIB-1 immunos taining was found in 50% and increased PCNA immunostaining in 75% of the sp ecimens displaying mild inflammation. Both antibodies had a 100% increased staining in specimens with moderate or severe inflammation. Increased proli feration as expressed by MIB-1 is thus better correlated with increasing de gree of dysplasia than is PCNA. Neither staining method is able to differen tiate neoplastic from inflammatory epithelial changes. However, in the abse nce of active inflammation, immunostaining for MIB-1 may be a valuable adju nct in the confirmation of dysplastic epithelial changes in long-standing u lcerative colitis, particularly in the indefinite changes category.