Comparison of flow cytometry and histology with mutational screening for p53 and Ki-ras mutations in surveillance of patients with long-standing ulcerative colitis

Background: We evaluate the usefulness of screening for p53 and Ki-ras muta tions in comparison with histological and flow cytometric findings. Methods : We analyzed 1486 biopsy samples from 769 locations of 83 patients with lo ng-standing ulcerative colitis enrolled in a surveillance program by means of histology, flow cytometry and SSCP analysis. As a control we used 66 bio psy samples of 16 patients with irritable bowel disease. Results: With resp ect to all biopsy samples analyzed, DNA aneuploidy was found in 32.5% (27/8 3) of patients, dysplasia in 22.9%. (15/83), p53 in 21.7% (18/83) and Ki-ra s mutations in 18.1% (15/83) of patients. None of these markers was found i n our control group. In 7 out of 10 patients who displayed dysplastic findi ngs during endoscopic surveillance p53 and / or Ki-ras mutations were prese nt in at least one colonoscopy. Statistically significant associations were observed between dysplasia and DNA aneuploidy (P < 0.001), between dysplas ia and p53 mutations (P = 0.05) and between dysplasia and p53 and/or Ki-ras mutations (P = 0.002). No significant associations were found between dysp lasia and Ki-ras mutations alone. The results for the SSCP analysis showed a much broader variation than those for the flow cytometric analysis. Concl usions: These results show that screening for p53 and Ki-ras mutations can be a useful adjunct in surveillance of patients with longstanding ulcerativ e colitis.