One of the antibodies, CM1, recognises p53 in formalin-fixed, paraffin-embedded archival material and using this reagent we found immunodetectable p53 in 28 of 124 (23%) pancreatic cancers.
Also in the light of the demonstrated cooperation of ras and p53 gene alterations in the transformation of cultured cells, our data suggest that p53 mutation is one of the genetic defects that may have a role in the pathogenesis of a proportion of pancreatic cancers.
These data support a role for p53 gene alterations in human pancreatic cancer, and suggest that loss of its regulatory functions may constitute one of the differences between pancreatic cancer and chronic pancreatitis.
Our results indicate that mutated K-ras and p53 genes can cooperate in the establishment of ductal pancreatic cancers, whereas other genetic events have to be present in nonductal tumors.
Although the rate of p53 mutations in pancreatic tumours is of the same order as in other adenocarcinomas (> or = 50%), an antibody response was found in only 5/78 (6.4%) sera from patients with pancreatic cancer.
Both failed to specifically suppress p53 protein production in a cell-free assay system or to have any effect on mutant p53 expression by human pancreatic cancer cell lines.
We determined the frequency of p53 protein overexpression and p53 point mutations in the conserved and nonconserved domains in pancreatic cancers as well as the coincidence of Ki-ras mutation in pancreatic ductal adenocarcinoma.
Nuclear accumulation of p53 correlates significantly with clinical features and inversely with the expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) in pancreatic cancer.
The detection of K-ras and p53 mutations, which occur in about 90 and 50% of pancreatic cancers, respectively, in blood, stool, or bile samples, seems to be a promising approach in the diagnosis.
A trend toward an association of p53 overexpression with poorer survival was found in patients with pancreatic cancers of the same grade, stage or with the same immunophenotype, but the data did not reach statistical significance.
From these, K-ras mutations detected in blood, stool and bile juice of patients at risk for pancreatic cancer seem to be more promising than p53 alterations as a more later step in carcinogenesis, although they are neither yet well established nor standardised by reliable assays.
This study confirms that loss of chromosomes, particularly chromosomes 17 and 18, which carry the p53 and DCC genes, are common in pancreas cancer.Chromosome 20 is also frequently lost.