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


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 p21waf1/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 p21waf1/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.
Noffsinger
A E
AE
Department of Pathology and Laboratory Medicine, University of Cincinnati Medical Center, Cincinnati, OH, USA. amy.noffsinger@uc.edu
Belli
J M
JM
Miller
M A
MA
Fenoglio-Preiser
C M
CM
D003093:Colitis, Ulcerative / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D004247:DNA; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2