Genetic abnormalities and expression of p53 in human colon carcinomas.

Genetic alteration and expression of p53 was examined on matched pairs of tumor and nonneoplastic tissues of colon carcinomas and compared with clinicopathological findings. Loss of heterozygosity (LOH) of p53 locus was found in 83% (44/53) of carcinomas and the incidence of LOH increased as tumor stage progressed. Among LOH cases, 63% (5/8) showed p53 mutations, most of which occured at CpG site. Although the level of p53 mRNA in tumor tissues was lower than its nonneoplastic counterpart in 55% (6/11) of the cases, no obvious relation was detected between mRNA expression and gene alteration. Accumulation of p53 protein determined by immunohistochemistry was found in 47% (25/53) of cases regardless of allelic status nor mRNA level. p53 immunoreactivity showed a tendency to increase with tumor stage. These results indicate the diversity of p53 alterations in the development and progression of colon carcinoma.