title: Telomerase and N-Cadherin Differential Importance in Adrenocortical Cancers and Adenomas.
abstract: Adrenocortical carcinomas (ACC) are most frequently highly aggressive tumors. We assessed the telomerase reverse transcriptase (TERT) and N-cadherin role in the biology of ACC and their potential utility as molecular biomarkers, in different types of tumoral adrenocortical tissue. A total of 48 adrenal cortex samples (39 tumoral and 9 normal adrenal glands) were studied. TERT promoter mutations were searched by PCR and Sanger sequencing in two hotspots positions (-124 and -146). Also, telomerase and N-cadherin expression were evaluated by immunohistochemistry. TERT promoter mutations were not detected in any of the samples either malignant or benign. Telomerase nuclear expression was present in 26.6% of ACC and in 45.5% of non-functioning adenomas. It was absent in benign Cushing's lesions and in normal adrenal glands. Contrarily, N-cadherin was always expressed in the cellular membranes of benign adenomas or normal adrenals but no expression was detected in the majority of ACC. Nuclear telomerase and membrane N-cadherin expression were positively correlated in ACCs. We conclude that in ACC, the loss of N-cadherin is a frequent phenomenon while the existence of TERT promoter mutations is not and nuclear telomerase expression is present in only a minority of cases. Since the loss of N-cadherin expression was identified in both high and low proliferative ACC, this marker should be considered important for diagnostic application. Our study also suggests the existence of a TERT non-canonical function in cell adhesion. J. Cell. Biochem. 118: 2064-2071, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Instituto de Investigação e Inovação em Saúde (I3S) da Universidade do Porto, R. Alfredo Allen, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal.|Department of Anatomy and UMIB (Unit for Multidisciplinary Research in Biomedicine) of ICBAS, University of Porto, R. de Jorge Viterbo Ferreira no. 228, 4050-313 Porto, Portugal.
authors.forename: Sofia S
authors.initials: SS
authors.lastname: Pereira
authors.affiliation: Instituto de Investigação e Inovação em Saúde (I3S) da Universidade do Porto, R. Alfredo Allen, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal.|Medical Faculty, Department of Pathology and Oncology, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
authors.forename: Valdemar
authors.initials: V
authors.lastname: Máximo
authors.affiliation: Instituto de Investigação e Inovação em Saúde (I3S) da Universidade do Porto, R. Alfredo Allen, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Coelho
authors.affiliation: Instituto de Investigação e Inovação em Saúde (I3S) da Universidade do Porto, R. Alfredo Allen, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Batista
authors.affiliation: Instituto de Investigação e Inovação em Saúde (I3S) da Universidade do Porto, R. Alfredo Allen, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal.|Medical Faculty, Department of Pathology and Oncology, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
authors.affiliation: Instituto de Investigação e Inovação em Saúde (I3S) da Universidade do Porto, R. Alfredo Allen, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal.
authors.forename: Susana G
authors.initials: SG
authors.lastname: Guerreiro
authors.affiliation: Instituto de Investigação e Inovação em Saúde (I3S) da Universidade do Porto, R. Alfredo Allen, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal.|Medical Faculty, Department of Pathology and Oncology, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal.|Department of Pathology, Hospital S. João, Alameda Prof. Hernâni Monteiro, Porto, Portugal.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sobrinho-Simões
authors.affiliation: Department of Anatomy and UMIB (Unit for Multidisciplinary Research in Biomedicine) of ICBAS, University of Porto, R. de Jorge Viterbo Ferreira no. 228, 4050-313 Porto, Portugal.
authors.forename: Mariana P
authors.initials: MP
authors.lastname: Monteiro
authors.affiliation: Instituto de Investigação e Inovação em Saúde (I3S) da Universidade do Porto, R. Alfredo Allen, 4200-135 Porto, Portugal.|Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal.|Department of Endocrinology, Hospital S. João, Alameda Prof. Hernâni Monteiro, Porto, Portugal.
authors.forename: Duarte
authors.initials: D
authors.lastname: Pignatelli
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D018268:Adrenocortical Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D019394:Ki-67 Antigen; C509186:TERT protein, human; D019098:Telomerase
keywords: ADRENAL GLAND; ADRENOCORTICAL TUMORS; N-CADHERIN EXPRESSION; TELOMERASE EXPRESSION; TERT PROMOTER MUTATIONS