Two hundred sixty-nine colorectal adenomas were examined for KRAS and BRAF mutation and immunohistochemical staining of β-catenin, O6-Methyl Guanine DNA Methyltransferase (MGMT), and p53.
Associations of Ki-ras proto-oncogene mutation and p53 gene overexpression in sporadic colorectal adenomas with demographic and clinicopathologic characteristics.
Our finding that two different p53 haplotypes are associated with colorectal adenoma and cancer, respectively, suggests that each of these haplotypes may independently impact on p53 function(s) within different genetic pathways of colorectal carcinogenesis.
Using comparative genomic hybridization and mutational analysis of APC, KRAS, and TP53 to evaluate 78 colorectal adenomas, we have shown that several of the significant relationships between gene mutations and chromosomal abnormalities reported in colorectal adenocarcinomas also exist at the adenomatous stage.
We screened the p53R2 gene coding regions and a regulatory region which contains a p53 binding sequence in 100 patients with colorectal adenoma and 100 control subjects using PCR, cold SSCP, and direct DNA sequencing.
A recent report suggests that a polymorphism of the p53 tumor suppressor gene that results in the substitution of a proline residue with an arginine residue at position 72 of the p53 protein might act as a risk factor in the malignant transformation of colorectal adenoma to cancer.
Polymerase chain reaction, single-strand conformation polymorphism and direct sequencing were used to analyze Ki-ras and p53 gene mutations in 73 sporadic colorectal adenomas: 28 LST; 22 IIa-type adenomas; and 23 polypoid adenomas.
In the index adenoma, p53 positivity was correlated with multiplicity at initial examination (P = 0.053), villous histology (P = 0.053), invasiveness of carcinoma (P < 0.003), and recurrence of colorectal adenomas (P = 0.025).
The authors analyzed the immunoreactivity for p53 protein (p53 protein expression), which reflects the functionally altered p53 gene, and K-ras mutations at codons 12 in 68 colorectal adenomas with both low-grade and high-grade dysplasia obtained from 62 patients.
We have addressed the intratumor heterogeneity of the mutational status of the k-ras oncogene and of the p53 oncosuppressor gene during the adenoma-carcinoma sequence by investigating 26 human colorectal adenomas containing early cancer.
We compared K-ras codon 12 and 13 gene mutations and p53 protein overexpression in 48 HNPCC (positive for Amsterdam criteria) and 59 sporadic colorectal adenomas, to examine whether they may represent similar or different molecular pathways to cancer.
Genetic progression in colorectal adenomas is heterogeneous, involving factors related to patient age and the presence of RER for the occurrence of ras mutations, but different intraindividual characteristics for the occurrence of p53 alterations and RER.
It appears that aneuploidy is linked with specific gene mutations, i.e., of the tumour suppressor gene p53 in chronic ulcerative colitis and in Barrett's esophagus, and of the protooncogene K-ras in colorectal adenomas.
Inactivation of the p53 tumor suppressor gene is considered to be a late event involved in the malignant transformation of colorectal adenoma to cancer.
These results indicate that p53 overexpression occurs early in the development of colorectal adenomas in FAP, whereas it is a late event in the development of sporadic tumors.
The sequential accumulation of genetic alterations characteristic of the colorectal adenoma-carcinoma sequence does not occur between adenoma and differentiated adenocarcinoma of the stomach, although adenomatous polyposis coll (APC) mutation in adenoma, and p53 mutation and loss of heterozygosity (LOH) of DCC (deleted in colorectal cancer) gene in carcinoma are prevalent genetic alterations.