The data indicate that constitutive activation of the Wnt signaling pathway caused by CTNNB1 mutation is involved in the development and/or progression of a subset of lung carcinoma, preferentially in adenocarcinoma.
We studied genetic alterations including loss of chromosome 18q (location of DCC, DPC4, and JV-18 genes), and mutations of the DPC4 (SMAD4) and beta-catenin genes in 28 appendiceal adenocarcinomas, consisting of 17 mucinous and 11 nonmucinous carcinomas.
In the current study, we investigated 60 sporadic colorectal adenocarcinomas along with adjoining and normal mucosa cases in humans for β-catenin mutations.
In squamous cell carcinomas more often multiple mutations per sample (p=0.040), and more PIK3CA (p=0.039) and CTNNB1 (p=0.038) mutations were detected compared to adenocarcinomas.
Our data show that large intragenic CTNNB1 mutations stabilize beta-catenin in small intestinal adenocarcinomas and influence the subcellular distribution of the protein.
These results show that genetic alterations of exon 3 of the beta-catenin gene do not occur and therefore do not contribute to the pathogenesis of esophageal adenocarcinomas.
Solid-pseudopapillary tumors of the pancreas are genetically distinct from pancreatic ductal adenocarcinomas and almost always harbor beta-catenin mutations.
The molecular mechanisms involved in the generation of epithelial ovarian cancers are poorly understood, but evidence suggests that the different histological subtypes may arise from independent tumorigenic events. beta-Catenin is emerging as an important oncogene in the transformation of a number of epithelial cancers, and mutations have been reported in a small study of endometrioid ovarian adenocarcinomas.
Tissue samples from 7 SPNs and 31 other pancreatic lesions (16 pancreatic ductal adenocarcinomas (PDAC), 11 pancreatic neuroendocrine tumors (PNET), 1 acinar cell carcinoma, 1 autoimmune pancreatitis lesion, and 2 focal pancreatitis lesions) were analyzed by NGS for mutations in exon 3 of CTNNB1.
We found that (a) aberrant methylation of Wnt antagonists is common in NSCLCs; (b) methylation of sFRP-2 is more prevalent in females, nonsmokers, and adenocarcinoma cases; (c) Dickkopf-3 methylation is significantly associated with a poor prognosis in adenocarcinomas; (d) there is a positive correlation between activated EGFR mutation and nuclear accumulation of beta-catenin; (e) KRAS mutation and aberrant methylation of Wnt antagonists are positively correlated; and (f) EGFR mutation is significantly associated with a good prognosis in tumors lacking methylated Wnt antagonist genes.
Aside from mutations in beta-catenin and lack of genetic changes common to pancreatic ductal adenocarcinomas, little is known about the chromosomal alterations in solid pseudopapillary neoplasms.
The results of this study strongly suggest that upregulation of the Wnt/β-catenin pathway is the major factor involved in the initial stages of the carcinogenesis of duodenal adenocarcinomas.
Among the several mechanisms involved in tumorigenesis, CagA and peptidoglycan of <i>H. pylori</i>, which enter the infected gastric epithelial cells play an important role by triggering oncogenic pathways.Inflammation induced by <i>H. pylori</i> in gastric epithelium, which involves the cyclooxygenase-2/prostaglandin E2 pathway and IL-1β, is also an important factor that triggers chronic active gastritis and adenocarcinoma.<i>H. pylori</i> infection induced oxidative stress and dysregulated E-cadherin/β-catenin/p120 interactions and function also play a critical role in tumorigenesis.
The immunohistochemical analysis of colon adenocarcinomas from clinical specimens revealed that beta-catenin and SMC3 antigens co-localize with maximal stain intensity within the transformed areas.
Activation of the wnt pathway through accumulation of beta-catenin may have a role in a subset of small intestinal adenocarcinomas but in contrast to colorectal carcinoma, accumulation of beta-catenin is generally not caused by inactivating APC or activating CTNNB1 mutations.
The aims of this study were (1) to compare protein expression of adenomatous polyposis coli (APC) gene, beta-catenin, and E-cadherin between proximal and distal gastric adenocarcinomas and (2) to investigate their use as markers of cancer risk in intestinal metaplasia (IM).
We sought to test this hypothesis by evaluating β-catenin immunoexpression in 44 sporadic microsatellite unstable adenocarcinomas and 44 MSS colon cancers.