DNA from eight carcinoma tissues and nine adenoma tissues from this reported case were examined for mutations in p53 by single strand conformation polymorphism analysis, K-ras by mutant allele specific analysis, and replication error or loss of heterozygosity of the TP53 locus on chromosome #17.
Homozygosity for an inactivating germ-line mutation of p53 had no effect on the incidence or the rate of progression of ApcMin/+-induced adenomas in mice and also did not affect the frequency of apoptosis in the cells of these adenomas.
This indicated that p53 point mutations may play a less crucial part in malignant conversion of adenoma to adenocarcinoma in the stomach than in the colon.
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.
As far as the possible loss of anti-oncogenes in pituitary tumors is concerned, gene alterations have not been found in the p53 nor in the retinoblastoma gene, while loss of chromosome 11q13 sequences, which contain the deduced location of the yet uncloned MEN-1 gene, has been reported in a subset of GH-secreting adenomas.
In the majority of the cases, p53 positive foci in the adenomas occurred in the most dysplastic areas, although focal positivity was detected in glands that were histologically normal.
Our data support the hypothesis that alterations of APC and p53 are responsible for most of the adenoma-carcinoma pathway, rather than TGF-beta RII alterations.
Twenty-eight colorectal carcinomas with invasion into submucosa or superficial muscularis propria without any adenoma component expressing immunoreactive p53 protein were selected from 168 resected specimens.
In order to investigate the role of p53 mutations in human thyroid tumours, DNA samples derived from fifty-six neoplastic tissues, ranging from benign adenomas to undifferentiated carcinomas, were examined for the presence of p53 gene mutations.
Our data suggest that in ampullary neoplasia 1) p53 mutations are common abnormalities associated with the transformation of adenomas and low-grade cancers into morphologically high-grade carcinomas, and 2) Ki-ras mutations are relatively less frequent and might be restricted to tumors originating from the bile duct component of the ampulla.
We have found that the expression of p53 messenger RNA is growth regulated in human cells following kinetics similar to that previously shown in mouse 3T3 cells, and is increased in the large majority of colon adenocarcinomas in comparison to adjacent normal mucosa and adenoma.
One of the two adenomas showing positive p53 nuclear staining was DNA aneuploid, and both were positive in PCNA staining, but their SPFs were low (2.1 and 3.3 per cent).
Cases of multiple synchronous adenomas showed different patterns of p53 expression but more positivity was found in adenomas from patients with a synchronous adenocarcinoma.
We compared the histopathological feature, mitotic index, proliferative activity (Ki-67 labeling index), expression of glycoproteins such as MUC2 mucin, sialyl Lewis A (SLe(a)) and sialyl dimeric Lewis X (SLe(x)), and p53 protein overexpression, between 108 adenomas in the old period (Group A, from 1969 to 1985) and 140 adenomas in the recent period (Group B, from 1995 to 1998).
Only one case of gall bladder cancer co-expressed the p53 and c-erbB-2, thereby suggesting that p53 and c-erbB-2 may have independent role in carcinogenesis of gall bladder cancer. c-erbB-2 over expression in adenoma and younger age group indicates its role as an early event in carcinogenesis of gallbladder.
Also, carcinoma cells with p53 mutations existing within adenoma tissues are detectable by immunostaining, even in formalin-fixed, paraffin-embedded specimens.
These findings suggest that p53 may be a target of chromosome 17 deletions and that this gene may play a role in the malignant transformation of adenomas.
These results suggest that other genetic mechanisms than those proposed for the classic adenoma-carcinoma sequence model can frequently underlie CRC development and that Ki-ras and p53 mutations should not be considered as universal markers for CRC.