Endocrine Abstracts

Background: Adrenocortical tumors (ACT) are classified as adenomas (ACA) or carcinomas (ACC). β-Catenin constitutive activation is a frequent alteration in benign and malignant ACT. E-cadherin was discovered as a protein associated with β-catenin which plays a crucial role in cadherin-mediated cell adhesion. N-cadherin seems to be involved in the development of malignant ACT, but information regarding expression of N-cadherin or E-cadherin in ACT is very limited.

Aim: To evaluate the expression of N-cadherin, E-cadherin and β-catenin in ACT and in ACC cell line models (H295R and SW13).

Methods: We analyzed differential expression of β-catenin, N-cadherin and E-cadherin by immunohistochemistry and by quantitative Real time-PCR in 71 sporadic ACT. This study included eight normal adrenal cortex samples (NA), 24 ACC, 18 aldosteronomas (APA), 23 cortisol producing adenomas (CPA), and 6 non-secreting incidentalomas (NSA).

Results: Real-time PCR: compared with NA, β-catenin was over-expressed in 50% of ACC (12/24) and 51% of ACA (24/47); N-cadherin was down-regulated in 75% of ACC (18/24) and in 60% of ACA (28/47).

IHC: 47% of ACC (7/15) and 33% of ACA (11/33) presented increased cytoplasmic and/or nuclear β-catenin accumulation; furthermore 100% of ACC (15/15) presented down-expression of N-cadherin and 18 of 33 ACA (55%) were down-regulated. We did not find expression of E-cadherin in any ACT. Interestingly, Spearman analysis showed correlation between β-catenin and N-cadherin expression (ACC vs ACA).

Conclusion: Our preliminary data suggest that β-catenin overexpression together with the aberrant expression of N-cadherin may participate to progression of ACT. Identification of these and other differentially expressed genes may enhance our understanding of the molecular biology of ACT development, and may contribute in creating new diagnostic and prognostic tools.