A unique basal pattern of p53 expression in ulcerative colitis is associated with mutation in the p53 gene

Aims: The p53 protein is implicated in the control of cell proliferation. differentiation, and death. As part of a study characterizing p53 alterations in colonic mucosa of patients with ulcerative colitis. we identified a unique pattern of basal p53 immunoreactivity. Methods and results: Tissue samples (n=180) from 42 ulcerative colitis patients were evaluated for p53 alterations by immunohistochemistry, loss of heterozygosity analysis. polymerase chain reaction-single-strand conformation polymorphism and direct sequencing. In addition. the expression of the p53-associated proteins p21(waf1/cip1) and MDM2 was evaluated immunohistochemically. Three basic patterns of p53 immunoreactivity were observed: (i) isolated immunoreactive cells in the crypt bases: (ii) strongly positive cells confined to the basal half of the glands: and (iii) diffusely staining cells. The basal staining pattern was observed in both non-neoplastic tissues and in some areas of dysplasia, and was associated with normal expression of p21(waf1/cip1) in all cases, and with p53 mutation in seven of 11 cases. Conclusions: The basal pattern of p53 expression is associated with mutation in the p53 gene, and appears to be an early change in a subgroup of ulcerative colitis patients. The significance of this pattern of immunoreactivity and the mechanism by which it develops are discussed.