The HNF-1α-mutated and inflammatory adenoma subgroups are more commonly seen in association with the OCP whereas there is an increased incidence of the β-catenin positive subtype with anabolic steroid use.
Consistent with the presence of WNT pathway gene alterations, all superficially serrated adenomas showed focal or diffuse nuclear β-catenin accumulation.
It occurred at the transition to dysplasia in serrated polyps with a significant increase in nuclear β-catenin labeling from sessile serrated adenomas (10%) to sessile serrated adenomas with dysplasia (55%) and traditional serrated adenomas (9%) to traditional serrated adenomas with dysplasia (39%) (P=0.0001).
Expression profiling revealed that ISC signatures, as well as the Wnt/β-catenin and Notch signaling pathways are downregulated in Ap4-deficient adenomas and intestinal organoids.
Delta ligands regulate Notch signaling in normal intestinal stem cells, while Jagged1 activates Notch in intestinal adenomas carrying active β-catenin.
In the present study, the expression of β-catenin, leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) and GATA6 was investigated during the transition from normal mucosa through to adenoma and adenocarcinoma in colorectal tissue sections obtained from 65 patients with a pathological diagnosis of colorectal adenocarcinoma and a history of adenoma.
The homeobox transcription factor PROX1 is induced by high Wnt/β-catenin activity in intestinal adenomas and colorectal cancer, where it promotes tumor progression.
Using human CRC cells harboring different Wnt/β-catenin pathway mutations in APC/KRAS or β-catenin/KRAS genes, and both genetic and pharmacological knockdown approaches, we show that oncogenic β-catenin signaling negatively regulates the expression of NHERF1 (Na<sup>+</sup>/H<sup>+</sup> exchanger 3 regulating factor 1), a PDZ-adaptor protein that is usually lost or downregulated in early dysplastic adenomas to exacerbate nuclear β-catenin activity.
Although a small subset of SLs are known to harbour TP53 mutations and Wnt/β-catenin pathway activation, suggesting that they may develop dysplasia or CRC via a 'chromosomal instability (CIN)-like' pathway, it is unclear if aneuploidy (characteristic of conventional adenoma) ever develops in SLs and is associated with development of dysplasia or CRC, in this context.
An identical CTNNB1 mutation was identified in the 1996 liver tumor together with a TERT promoter mutation showing that this hepatocellular carcinoma results from the malignant transformation of the initial β-catenin inflammatory adenoma.
In addition to these specific pathways, the Wnt/β-catenin pathway appears to play an important role in adrenal tumorigenesis, because β-catenin mutations have been identified in both aldosterone- and cortisol-producing adenomas.
Our purpose was the evaluation of microsatellite stability status within conventional colon adenomas and also β-catenin, BRAFV600E and p53 contribution.
Four APAs showed a predominant (≥50%) zona fasciculata-like cell pattern: one tumor had CYP11B1 H-score = 150, no detectable CYP11B2 expression, and harbored a PRKACA p.Leu206Arg mutation (that we have reported previously elsewhere), one had no CYP11B1 expression, CYP11B2 H-score = 40, and no mutations; the remaining two adenomas had high CYP11B1 H-score (160 and 240, respectively) and low CYP11B2 H-score (30 and 15, respectively), with the latter harboring a CTNNB1p.Ser45Phe activating mutation.
Sequencing analyses identified APC or CTNNB1 mutations in the majority of sporadic adenomas (58/84, 69%) and MMR-proficient Lynch syndrome-associated adenomas (13/18, 72%).
The lower apoptotic activity of low-grade slightly elevated adenomas can be partly attributed to upregulated β-catenin pathway activity and downregulated c-Myc expression.
We sequenced PRKACA, GNAS and CTNNB1 genes in 108 patients, including 60 patients with CPAs (57 with unilateral and three with bilateral adenomas), 13 with nonfunctional adenomas, 12 with adrenocortical carcinomas (ACCs), 15 with primary bilateral macronodular hyperplasia (PBMAH) and eight with aldosterone and cortisol cosecreting adenomas.
Their aldosterone-producing adenomas harbored activating mutations of CTNNB1, encoding β-catenin in the Wnt cell-differentiation pathway, and expressed LHCGR and GNRHR, encoding gonadal receptors, at levels that were more than 100 times as high as the levels in other aldosterone-producing adenomas.
We report a case of a well-differentiated hepatocellular neoplasm with Dubin-Johnson-like pigment displaying histological features overlapping with a beta-catenin mutated inflammatory adenoma and a well-differentiated hepatocellular carcinoma in a non-cirrhotic liver.