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Tumour Biol. 2016 Oct;37(10):13545-13555. Epub 2016 Jul 28.

Investigation of N-cadherin/β-catenin expression in adrenocortical tumors.

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Division of Endocrinology, Department of Medicine (DIMED), University of Padua, via Ospedale Civile, 105, 35128, Padua, Italy.
Division of Endocrinology, Department of Medicine (DIMED), University of Padua, via Ospedale Civile, 105, 35128, Padua, Italy.
Department of Molecular Medicine, University of Padova, via Marzolo 3, 35131, Padova, Italy.
Division of Minimally Invasive Endocrine Surgery, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
Division of Pathology and Cytopathology, Department of Medicine (DIMED), University of Padua, Padua, Italy.


β-catenin is a multifunctional protein; it is a key component of the Wnt signaling, and it plays a central role in cadherin-based adhesions. Cadherin loss promotes tumorigenesis by releasing membrane-bound β-catenin, hence stimulating Wnt signaling. Cadherins seem to be involved in tumor development, but these findings are limited in adrenocortical tumors (ACTs). The objective of this study was to evaluate alterations in key components of cadherin/catenin adhesion system and of Wnt pathway. This study included eight normal adrenal samples (NA) and 95 ACT: 24 adrenocortical carcinomas (ACCs) and 71 adrenocortical adenomas (ACAs). β-catenin mutations were evaluated by sequencing, and β-catenin and cadherin (E-cadherin and N-cadherin) expression was analyzed by quantitative reverse transcription PCR (qRT-PCR) and by immunohistochemistry (IHC). We identified 18 genetic alterations in β-catenin gene. qRT-PCR showed overexpression of β-catenin in 50 % of ACC (12/24) and in 48 % of ACA (21/44). 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. N-cadherin downregulation has been found in 83 % of ACC (20/24) and in 59 % of ACA (26/44). Similar results were obtained by IHC: N-cadherin downregulation was observed in 100 % (15/15) of ACC and in 55 % (18/33) of ACA. β-catenin overexpression together with the aberrant expression of N-cadherin may play important role in ACT tumorigenesis. The study of differentially expressed genes (such as N-cadherin and β-catenin) may enhance our understanding of the biology of ACT and may contribute to the discovery of new diagnostic and prognostic tools.


Adrenocortical carcinomas; Adrenocortical tumors; N-cadherin; Wnt/beta-catenin signaling pathway

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