As PCR-SSCP analysis is a convenient method to detect point mutation, we have now examined 24 colorectal cancers for the p53 gene by this method, and detected the mutations.
Allelic loss was studied for chromosomes 5, 17, and 18, and immunohistochemical analysis was done of the p53 protein product in tumors from 91 patients with colorectal cancer.
The increased expression of Rb and p53 RNA was observed in a majority of colorectal cancers in comparison to adjacent normal mucosa and is accompanied by proportional increase in the expression of histone H3 gene.
We have analyzed the loss of heterozygosity of the human p53 tumor suppressor gene in 40 cases of colorectal carcinoma using two restriction fragment length polymorphisms detected by BglII and AccII restriction enzymes. p53 gene product expression was studied immunohistochemically in 64 colorectal carcinomas, 18 adenomas, and 40 normal colonic mucosae using an anti-human p53 monoclonal antibody (Pab 1801) and the avidin-biotin-peroxidase complex technique.
Results suggested that aberrations of the p53 gene were not correlated with the malignancy of some types of brain tumors such as anaplastic astrocytoma and glioblastoma, contrary to previous observations on colorectal cancers.
This dual parameter flow cytometric method, evaluating both DNA ploidy and p53 expression, may prove useful in identifying different biological subgroups of colorectal cancer.
In colorectal carcinoma, it has been shown that the accumulation of several alterations in ras genes and p53 genes is most important for the conversion of adenoma to carcinoma.
The positive effect on cell proliferation by these mutant p53 proteins is consistent with a role for activated p53 mutants in the genesis of colorectal carcinomas.
Eleven different missense and one nonsense mutant-type p53 cDNAs, which have been frequently detected in human colorectal carcinomas, were constructed and examined for their ability to cooperate with activated human H-ras genes, pSK2 and pHs49, in transfection of rat embryo fibroblasts (REF).
Surprisingly, given the proposed role for loss of function mutations of the p53 gene in the development of human colorectal cancer, we have found no evidence for either an increase in the rate of adenoma formation in APC +/-, p53 -/- animals, or an increased rate of progression to malignancy compared with APC +/- p53 +/+ mice.
Three p53 DNA polymorphisms (BstU I and Msp I restriction fragment length polymorphisms (RFLPs) in exon 4 and intron 6 respectively, and a 16 bp duplication in intron 3) and their haplotype combinations were studied in patients with colorectal cancer and compared with patients with ulcerative colitis and healthy controls.
Pgp expression was not associated with either p53 expression (P = 0.73) or incidence of p53 gene mutation (P = 0.70), suggesting that mutant p53 does not induce Pgp overexpression in colorectal carcinomas.
A total of 94 paraffin-embedded tissue specimens from patients with colorectal cancer were analysed. p53 gene mutations were detected in 40.0% (12/30) of de novo cancer, 36.7% (11/30) of polyp-forming cancer, and 44% (15/34) of advanced cancer. p53 mutations were detected at a high frequency in both types of early colorectal cancer as well as in advanced cancer.