Comparison of Flow Cytometry and Histology with Mutational Screening for p53 and Ki-ras Mutations in Surveillance of Patients with Long-standing Ulcerative Colitis

Abstract

Background: We evaluate the usefulness of screening for p53 and Ki-ras mutations in comparison with histological and flow cytometric findings. Methods: We analyzed 1486 biopsy samples from 769 locations of 83 patients with long-standing ulcerative colitis enrolled in a surveillance program by means of histology, flow cytometry and SSCP analysis. As a control we used 66 biopsy samples of 16 patients with irritable bowel disease. Results: With respect to all biopsy samples analyzed, DNA aneuploidy was found in 32.5% (27/83) of patients, dysplasia in 22.9% (15/83), p53 in 21.7% (18/83) and Ki-ras mutations in 18.1% (15/83) of patients. None of these markers was found in our control group. In 7 out of 10 patients who displayed dysplastic findings during endoscopic surveillance p53 and / or Ki-ras mutations were present in at least one colonoscopy. Statistically significant associations were observed between dysplasia and DNA aneuploidy ( P < 0.001), between dysplasia 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 dysplasia and Ki-ras mutations alone. The results for the SSCP analysis showed a much broader variation than those for the flow cytometric analysis. Conclusions: These results show that screening for p53 and Ki-ras mutations can be a useful adjunct in surveillance of patients with longstanding ulcerative colitis.

• Flow Cytometry Ki-RAS P53 Ulcerative Colitis