Ba. Lashner et al., Evaluation of the usefulness of testing for p53 mutations in colorectal cancer surveillance for ulcerative colitis, AM J GASTRO, 94(2), 1999, pp. 456-462
Objective: Immunohistochemical staining for p53 suppressor gene mutations i
s sensitive and, therefore, has potential for use as a complementary test f
or dysplasia to improve ulcerative colitis (UC) cancer surveillance program
performance. Methods: A cohort of 95 patients with long standing pan-UC en
rolled in a surveillance program was studied. Archival colonic biopsy speci
mens were stained for p53 mutations and clinical information was obtained f
rom medical records. Results: The 37 patients who developed p53 mutations w
ere significantly more likely to develop dysplasia or cancer (relative risk
[RR] 4.53, 95% confidence interval [CI] 2.16-9.48). The p53 mutations deve
loped approximately 8 months before low grade dysplasia, 26 months before h
igh grade dysplasia, and 38 months before cancer. Three of seven cancer pat
ients 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 a
ssociated with cancer-related mortality, and 3) may possibly be prevented b
y folic acid supplementation. (Am J Gastroenterol 1999;94:456-462. (C) 1999
by Am. Coll. of Gastroenterology).