p53 mutations in colorectal cancer.

TLDR

Mutation of the p53 gene is one of the most common genetic changes in the development of human colorectal cancer. The study aimed to determine the molecular basis of p53 overexpression by examining its expression in 10 colorectal cancer cell lines. The authors evaluated p53 protein levels in these cell lines using ELISA, cell staining, immunoprecipitation, and sequencing of p53 cDNA to detect mutations. Immunohistological staining revealed p53 overexpression in about 50 % of primary colorectal carcinomas but none in benign adenomas, and in cell lines high p53 expression corresponded to mutant p53 mRNA while even low‑expressing lines harbored point mutations, showing that overexpression is synonymous with mutation yet not all mutations are detectable by immunohistochemistry.

Abstract

Immunohistological staining of primary colorectal carcinomas with antibodies specific to p53 demonstrated gross overexpression of the protein in approximately 50% of the malignant tumors examined. Benign adenomas were all negative for p53 overexpression. To determine the molecular basis for this overexpression we examined p53 protein expression in 10 colorectal cancer cell lines. Six of the cell lines expressed high levels of p53 in ELISA, cell-staining, and immunoprecipitation studies. Direct sequencing and chemical-mismatch-cleavage analysis of p53 cDNA by using the polymerase chain reaction in these cell lines showed that all cell lines that expressed high levels of p53 were synthesizing mRNAs that encoded mutant p53 proteins. In two of those four cell lines where p53 expression was lower, point mutations were still detected. Thus, we conclude that overexpression of p53 is synonymous with mutation, but some mutations would not be detected by a simple immunohistochemical analysis. Mutation of the p53 gene is one of the commonest genetic changes in the development of human colorectal cancer.