Telomerase and N-Cadherin Differential Importance in Adrenocortical Cancers and Adenomas

J Cell Biochem. 2017 Aug;118(8):2064-2071. doi: 10.1002/jcb.25811. Epub 2017 Apr 21.

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.

Keywords: ADRENAL GLAND; ADRENOCORTICAL TUMORS; N-CADHERIN EXPRESSION; TELOMERASE EXPRESSION; TERT PROMOTER MUTATIONS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / genetics
  • Adenoma / metabolism
  • Adenoma / surgery
  • Adrenal Cortex Neoplasms / genetics*
  • Adrenal Cortex Neoplasms / metabolism
  • Adrenal Cortex Neoplasms / pathology
  • Adrenal Cortex Neoplasms / surgery
  • Adrenocortical Carcinoma / genetics*
  • Adrenocortical Carcinoma / metabolism
  • Adrenocortical Carcinoma / pathology
  • Adrenocortical Carcinoma / surgery
  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Case-Control Studies
  • Cell Membrane / metabolism
  • Cell Nucleus / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / surgery
  • Promoter Regions, Genetic
  • Telomerase / genetics*
  • Telomerase / metabolism

Substances

  • Antigens, CD
  • CDH2 protein, human
  • Cadherins
  • Ki-67 Antigen
  • TERT protein, human
  • Telomerase