17 colorectal carcinomas without any adenoma component expressing both immunoreactive p53 and BGP protein were selected from 96 resected specimens from our previous study.
A mutation of the K-ras gene was detected in nine (47%) of 19 hyperplastic polyps, and five (56%) of nine adenomas. p53 protein nuclear accumulation was detected immunohistochemically in two (22%) of nine adenomas, but not in any of the hyperplastic polyps.
Aberrant expression of p53 was uncommon overall, but occurred more frequently in MPs and SAs (12%) than adenomas (1%) (P < 0.04) and there was concordant loss of expression of MGMT.
Accumulation of ras and p53 alterations occurs during the adenoma/dysplasia-carcinoma sequence in small intestinal carcinogenesis, but a ras-independent pathway may also exist.
All carcinomas arising from p53-positive adenomas were also p53 positive. p53 positivity associated with a higher MVD in adenomas (P = 0.02), but not in carcinomas (P = 0.78).
Also, carcinoma cells with p53 mutations existing within adenoma tissues are detectable by immunostaining, even in formalin-fixed, paraffin-embedded specimens.
Alterations of APC, KRAS and TP53 were observed in a higher percentage of adenocarcinomas compared to adenomas (P<0.05) indicating that the alterations accumulated with malignancy.
Although gene-to-gene analyses identified genetic alterations such as APC, KRAS and TP53 mutations in colon adenomas, it is largely unknown whether there are any others in them.
Apoptosis was also significantly lower in serrated than in tubulovillous adenomas, but higher than in hyperplastic polyps. p53 oncoprotein expression was significantly greater in both serrated and tubulovillous adenomas than in hyperplastic polyps. bcl-2 protein expression was higher only in tubulovillous adenomas.
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.
Cases of multiple synchronous adenomas showed different patterns of p53 expression but more positivity was found in adenomas from patients with a synchronous adenocarcinoma.
Clinicopathologic characteristics, Ki-ras mutational status, and overexpression of p53 protein were compared in 25 NA tumors and 55 flat adenomas without a central depression (flat tumor).
Combining our data on adenomas with data already published and in comparison with the spectrum of mutations in colorectal carcinomas, it is suggested that some p53 mutations have a weaker effect than others and are therefore more likely to be found in adenomas which have not progressed to carcinomas.