Numerous specific targets were explored for the treatment of ACC, such as those involving angiogenesis, steroidogenesis, Wnt/β-catenin pathway and many others key factors.
Genetic analysis of MEN1 and other ACC associated genes, loss of heterozygosity (LOH) of MEN1 locus, immunohistochemistry staining of menin, P53 and β-catenin in ACC tissue were performed.
Immunostaining with trypsin/chymotrypsin, negativity of beta-catenin help in the differential; as a caveat, neuroendocrine differentiation is common in ACCs.
In conclusion, the discovery of novel large deletions in addition to the point mutations in CTNNB1 infers that activation of Wnt/β-Catenin pathway via alterations in CTNNB1 occurs frequently in ACCs.
Twenty-four PAs (15 cell-rich and 9 cell-poor tumors) and 24 ACCs (10 tubular, 8 cribriform, and 6 solid tumors) were selected for the analysis of β-catenin distribution and cellular localization.
These findings suggest that BCL9 overexpression may serve as an alternative driver of constitutive Wnt/β-Catenin activation in ACC and could represent a potential molecular and diagnostic marker of tumor malignancy.
We performed immunohistochemical staining for β-catenin and mutation analysis for Wnt/β-catenin-related genes (CTNNB1, APC, AXIN1 and AXIN2) in BCA (n = 34), BCAC (n = 3), ACC (n = 67) and PA (n = 31).
We verified that Nutlin-3a inhibited cellular proliferation in ACC cell line NCI-H295R which harbored CTNNB1 mutation but not in SW13 cells which did not.
The Wnt/beta-catenin pathway can be activated in both benign and malignant tumors by <i>CTNNB1</i> mutations and by <i>ZNRF3</i> inactivation in adrenal cancer (ACC).
This study aimed to explore the effect of MED27 on the expression of epithelial-mesenchymal transition (EMT)-related proteins and β-catenin in adrenal cortical carcinoma (ACC).
IHC data were in accordance with qRT-PCR results: 47 % of ACC (7/15) and 33 % of ACA (11/33) showed increased cytoplasmic or nuclear β-catenin accumulation.
We performed exome sequencing and SNP array analysis of 45 ACCs and identified recurrent alterations in known driver genes (CTNNB1, TP53, CDKN2A, RB1 and MEN1) and in genes not previously reported in ACC (ZNRF3, DAXX, TERT and MED12), which we validated in an independent cohort of 77 ACCs.
Evaluation of adrenal tumors from 118 adult patients demonstrated an increase in CTNNB1 mutations and abnormal β-catenin accumulation in both adrenocortical adenoma and ACC.
Within this dataset, the expression profiles of five genes were validated by real time-PCR (RT-PCR) in a cohort of 34 adrenocortical tissues (six AA and one ACC with CTNNB1 mutations, 13 AA and four ACC with WT CTNNB1, and 10 normal adrenal glands) and two human ACC cell lines.