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


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Abstract

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 [Cl] 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 37vs0 of 58,p< 0.03). Folic acid supplementation had a small, significant protective effect for p53 mutations (RR 0.97, Cl 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.

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