title: Investigation of N-cadherin/β-catenin expression in adrenocortical tumors.
abstract: 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.
authors.affiliation: Division of Endocrinology, Department of Medicine (DIMED), University of Padua, via Ospedale Civile, 105, 35128, Padua, Italy. beatrice.rubin.1@unipd.it.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Rubin
authors.affiliation: Division of Endocrinology, Department of Medicine (DIMED), University of Padua, via Ospedale Civile, 105, 35128, Padua, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Regazzo
authors.affiliation: Department of Molecular Medicine, University of Padova, via Marzolo 3, 35131, Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Redaelli
authors.affiliation: Department of Molecular Medicine, University of Padova, via Marzolo 3, 35131, Padova, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Mucignat
authors.affiliation: Division of Minimally Invasive Endocrine Surgery, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
authors.forename: Marilisa
authors.initials: M
authors.lastname: Citton
authors.affiliation: Division of Minimally Invasive Endocrine Surgery, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Iacobone
authors.affiliation: Division of Endocrinology, Department of Medicine (DIMED), University of Padua, via Ospedale Civile, 105, 35128, Padua, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Scaroni
authors.affiliation: Division of Endocrinology, Department of Medicine (DIMED), University of Padua, via Ospedale Civile, 105, 35128, Padua, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Betterle
authors.affiliation: Division of Endocrinology, Department of Medicine (DIMED), University of Padua, via Ospedale Civile, 105, 35128, Padua, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Mantero
authors.affiliation: Division of Pathology and Cytopathology, Department of Medicine (DIMED), University of Padua, Padua, Italy.
authors.forename: Ambrogio
authors.initials: A
authors.lastname: Fassina
authors.affiliation: Division of Endocrinology, Department of Medicine (DIMED), University of Padua, via Ospedale Civile, 105, 35128, Padua, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Pezzani
authors.affiliation: Division of Endocrinology, Department of Medicine (DIMED), University of Padua, via Ospedale Civile, 105, 35128, Padua, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Boscaro
mesh_terms: D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000311:Adrenal Glands / Q000378:metabolism / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C050361:CDH2 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; D012333:RNA, Messenger; D051176:beta Catenin
keywords: Adrenocortical carcinomas; Adrenocortical tumors; N-cadherin; Wnt/beta-catenin signaling pathway