Evaluation of The Usefulness of Testing for P53 Mutations in Colorectal Cancer Surveillance for Ulcerative Colitis

OBJECTIVE: Immunohistochemical staining for p53 suppressor gene mutations is sensitive and, therefore, has potential for use as a complementary test for dysplasia to improve ulcerative colitis (UC) cancer surveillance program performance. METHODS: A cohort of 95 patients with long standing pan-UC enrolled in a surveillance program was studied. Archival colonic biopsy specimens were stained for p53 mutations and clinical information was obtained from medical records. RESULTS: The 37 patients who developed p53 mutations were significantly more likely to develop dysplasia or cancer (relative risk RR 4.53, 95% confidence interval CI 2.16-9.48). The p53 mutations developed approximately 8 months before low grade dysplasia, 26 months before high grade dysplasia, and 38 months before cancer. Three of seven cancer patients with p53 mutations had Dukes' stage C or D, whereas only one of five cancer patients without p53 mutations had Dukes' C or D; all three patients who died from metastatic cancer had p53 mutations (three of 37 vs 0 of 58, p < 0.03). Folic acid supplementation had a small, significant protective effect for p53 mutations (RR 0.97, CI 0.94-1.00). CONCLUSION: p53 Mutations 1) are associated with, and likely precede, dysplasia and cancer, 2) are associated with cancer-related mortality, and 3) may possibly be prevented by folic acid supplementation.