Cooperative genetic aberrations involving APC (adenomatous polyposis coli), beta-catenine, K-ras, and p53 are involved in the multistep adenoma-carcinoma sequence of CRC.
Cytokeratin 7 and especially cytokeratin 17 highlighted the presence of ducts in the hyperplastic lesion, which are not present in adenomas. p16 and p53 were negative and Ki-67 immunostaining demonstrated similar low proliferation indices for normal and hyperplastic glands.
Despite the aggressive features of massive size and cavernous sinus invasion, mitotic rates and immunohistochemistry (IHC) labeling for p53 and MIB-1, features alleged to be associated with atypical adenomas, were minimally increased.
DNA analysis revealed allele loss on chromosome 17 (17p13, near the locus of p53 tumour suppressor gene) in the hepatocellular carcinoma but not in the adenoma.
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.
EBV incorporation was revealed in 1 (1.5%) of the adenoma-carcinomas, in none of the adenomas, and in 17 (5.6%) of the de novo carcinomas. p53 overexpression was observed in 24.2% (16 of 66) of the adenomas in the adenoma-carcinoma cases and in 36.5% (23 of 63) of corresponding carcinomas (kappa = 0.63, P = 0.00).
Expression of p53 and PCNA were detected by immunocytochemistry in paraffin-embedded sections of infiltrating duct carcinoma and control breast tissue (normal tissue and adenoma).
Five specific "malignant" events (gain of 8q, 13q, and 20q and loss of 17p and 18q) and aberrant staining for p53 and SMAD4 were all increased in the adenoma fractions of carcinoma cases compared with pure adenomas.
Formalin Fixed Paraffin Embedded tissue were studied for miRNA expression, KRAS, BRAF, PIK3CA mutations, and immuno-histochemistry for APC and p53 proteins for normal colon (n=11), hyperplastic polyps (n=11), high grade adenomas (n=10), low grade adenomas (n=34) and adenocarcinoma (n=13).
Hence, as "adenoma-carcinoma sequence" model of development of colorectal carcinoma, inactivation of the APC and p53 genes appear to be involved in development of the de novo type of colorectal carcinoma even though the adenoma stage is not observed.
Histone modifications have been linked to increased p53 expression and longer progression-free survival in pituitary tumors; sirtuins are expressed at higher values in GH-expressing compared to nonfunctional adenomas and correlate inversely with size in somatotrophs.
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.
However, induction of apoptosis, associated with increased p53 protein expression but not with changes in Bcl-2 expression, was only detected in the adenoma derived BH/C1 and AA/C1 cell lines which express wild type p53 activity.
Immunohistochemical patterns of p53 and beta catenin were studied using the natural carcinogenetic model of malignant colorectal sporadic adenoma in 27 formalin-fixed paraffin-embedded polyps.
Immunohistochemical results strongly correlate with the SSCP results: p53 protein was positive in tumors with p53 mutation but not in others; 32% of studied adenomas had detectable HPV16 DNA, while 53% of carcinomas were HPV16+.Among these I presented a p53 mutation.No HPV18 E6 sequence could be detected.
Immunostains for AFP and beta-catenin were negative in both the hepatic adenomas and areas of hepatocellular carcinoma. p53 immunostaining was positive within the areas of malignant transformation in one case.
In addition, NCOA3, MYC, EGFR, and RAB20 amplifications, as well as TP53 deletions correlated with increased DNA stem line values and/or aneuploidy in adenomas (P<0.05).
In addition, the mutations of p53 for the adenomatous components of the adenomas containing early cancer were statistically significantly associated with severe dysplasia (p-value = 0.01).