In all eight patients, beta-catenin was immunostained at the membranes of the cell-to-cell borders in normal epithelial cells, whereas the nuclei and cytoplasms stained intensely in addition to the membranes in both adenoma and cancer cells. beta-Catenin expression levels in tumor tissues were over three times higher than those in corresponding normal mucosae of all of the three patients, whose resected specimens were available for quantitative immunoblot analysis.
We searched for alterations in the APC mutation cluster region, the whole coding regions of TGF-beta type II receptor (RII) and beta-catenin exon 3 in 16 cases of cancer in adenomas of the colon.
Results suggest that modulation of aberrant beta-catenin expression occurs during NSAID-induced regression of intestinal adenomas and that Bcl-2 may confer resistance to these effects.
Small adenomas with beta-catenin mutations do not appear to be as likely to progress to larger adenomas and invasive carcinomas as other adenomas, however, with the result that beta-catenin mutations are only rarely seen in invasive cancers.
Immunohistochemical methods were used to determine the relationship between APC and beta-catenin protein expression in human colonic tissues (150 normal, 9 hyperplastic, 58 adenomas and 83 carcinomas) and 12 paired samples of normal and cancer tissue in mouse colon.
These data support the following hypotheses derived from sporadic colorectal tumors: beta-catenin mutations are generally an alternative to mutations at APC, MSI is not usually an early phenomenon in colorectal tumorigenesis, and K-ras mutations are more typical of large- and moderate-sized adenomas.
We evaluated the cellular localization of beta-catenin in thyroid carcinomas associated (n = 4) or not associated (n = 173) with FAP, since loss of functional protein of the adenomatous polyposis coli (APC) gene leads to nuclear accumulation of beta-catenin in adenomas and carcinomas of the FAP colon.
There was less loss of membranous beta-catenin staining and less nuclear beta-catenin accumulation in resistant adenomas compared with baseline adenomas from the same (sulindac-resistant) patients (P < 0.01) or baseline adenomas from responsive patients (P < 0.01).
Because alterations of the adenomatous polyposis coli (APC) gene are present in biliary tract cancers and the APC protein modulates levels of beta-catenin, we evaluated the role of beta-catenin in biliary tract cancer by sequencing the third exon of the beta-catenin gene among 107 biliary tract cancers and 7 gallbladder adenomas from a population-based study in CHINA: Point mutations of serine or threonine phosphorylation sites in exon 3 of beta-catenin were present in 8 of 107 (7.5%) biliary tract cancers and 4 of 7 (57.1%) gallbladder adenomas.
The results of the current study suggest that up-regulation of the Wnt signaling pathway, including accumulation of mutant CTNNB1 in the nuclei, plays an important role in the tumorigenesis and development of adenoma in the pituitary gland.
An important role for beta-catenin pathways in colorectal carcinogenesis was first suggested by the protein's association with adenomatous polyposis coli (APC) protein, and by evidence of dysregulation of beta-catenin protein expression at all stages of the adenoma-carcinoma sequence.
Adenomas and carcinomas showing both nuclear and reduced membranous expression of beta-catenin, compared with those with normal membranous expression, tended to show allele loss ( P<0.01).
Altered expression of beta-catenin, such as nuclear or cytoplasmic expression and loss of membranous expression, was also significantly higher in adenomas than in dysplasias or carcinomas (p <0.001).
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.