All evaluated molecules were significantly lower in IBD patients, of which cytochrome c and p53 were significantly lower exclusively in patients with Crohn's disease (CD) and cytochrome c differed significantly between CD and ulcerative colitis (UC).
In the present study, ATF3, p53, and p53 target gene Bax expression increased in CD patients; a mouse 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced CD model; and a TNF-α-treated HT29 cell colitis model.
Mutations in the tumor suppressor gene p53 are associated with neoplasia in ulcerative colitis, but little is understood of their significance in Crohn's disease (CD).
Mutations in the tumor suppressor gene p53 are associated with neoplasia in ulcerative colitis, but little is understood of their significance in Crohn's disease (CD).
Colonic lavage fluid from 190 patients with ulcerative colitis (73), Crohn's disease (58) or controls (49 non-tumour, 10 colorectal cancer) was studied by oligomer-specific hybridization for K-ras mutations and single-strand conformation polymorphism (SSCP) for p53 mutations.
In conclusion, enhanced epithelial cell proliferation, p53 overexpression, and decrease of p21(WAF1/CIP1) expression may predispose the small-bowel mucosa to dysplasia and carcinoma development in Crohn disease.
Overexpression of p53 gene product and/or 17p allelic loss were present in 47% of sporadic carcinomas and 33% of contiguous adenomas and in 71% of Crohn's-associated carcinomas and 43% of dysplasias.
In comparison to the 41 RER-negative proximal colonic cancers, RER-positive cancers had more frequent exophytic growth (P = 0.04), large size (P = 0.03), poor differentiation (P = 0.0004), extracellular mucin production (P = 0.003) and Crohn's-like lymphoid reaction (P = 0.003), and a trend toward less frequent p53 gene product overexpression by immunohistochemistry (3/17, 18%, versus 18/41, 44%, P = 0.06).