Expression of proliferating cell nuclear antigen (PCNA) and Ki-67 in dysplasia in inflammatory bowel disease

Objective: Previous studies have revealed large variations in the interobserver agreement of dysplasia grading in inflammatory bowel disease. Therefore, we investigated the diagnostic value of two novel monoclonal antibodies (MIB 1 against Ki-67 and PC 10 against PCNA) in the detection of dysplasia. Methods: A total of 62 biopsies were investigated and histologically classified as follows: 13 probably positive for dysplasia; 15 low-grade dysplasia; five high-grade dysplasia; and 15 inflammation without dysplasia and 14 normal controls. The percentage of positive Ki-67- or PCNA-stained nuclei (=labelling index) was determined in relation to the distribution throughout the mucosa. Results: In all biopsies PCNA-labelling index exceeded that oi Ki-67-labelling index. In the superficial half of the crypt PCNA- and Ki-67-labelling indices in the biopsies with indefinite for dysplasia, probably positive or low-grade dysplasia exceeded that of normal tissue (P<0.001). However, an unequivocal discrimination between biopsies with 'indefinite for dysplasia, probably positive' or low-grade dysplasia and inflammation was not possible. PCNA- land Ki-67-labelling indices were significantly higher in high-grade than in low-grade dysplasia (PCNA 81.4% vs. 44.3%, Ki-67 54.8% vs 30.9%, P<0.001). Most interestingly, labelling indices of both markers were significantly (P<0.0001) higher in biopsies with high-grade dysplasia than with active inflammation in the superficial half of the crypt. Conclusion: PCNA and Ki-67 are useful adjuncts in the diagnosis of high-grade dysplasia, because high-grade dysplasia can easily be distinguished from low-grade dysplasia or active inflammation if the distribution of the positive-stained cells within the mucosa is taken into account. Lower unspecific binding and lower influence on proliferation activity by inflammation prompts us to prefer Ki-67 (MIB 1).