title: Differential expression of microRNA-675, microRNA-139-3p and microRNA-335 in benign and malignant adrenocortical tumours.
abstract: BACKGROUND
  For the clinical management of adrenocortical neoplasms it is crucial to correctly distinguish between benign and malignant tumours. Even histomorphologically based scoring systems do not allow precise separation in single lesions, thus novel parameters are desired which offer a more accurate differentiation. The tremendous potential of microRNAs (miRNAs) as diagnostic biomarkers in surgical pathology has recently been shown in a broad variety of tumours.
  
  
  METHODS
  In order to elucidate the diagnostic impact of miRNA expression in adrenocortical neoplasms, a cohort of 20 adrenocortical specimens including normal adrenal tissue (n=4), adrenocortical adenomas (ACAs) (n=9), adrenocortical carcinomas (ACCs) (n=4) and metastases (n=3) was analysed using TaqMan low density arrays to identify specific miRNA profiles in order to distinguish between benign and malignant adrenocortical lesions. Results were validated in a validation cohort (n=16).
  
  
  RESULTS
  Concerning the differential diagnosis of ACAs and ACCs, 159 out of 667 miRNAs were up- and 89 were down-regulated in ACAs. Using real-time PCR analysis of three of the most significantly expressed single key miRNAs allowed separation of ACAs from ACCs. ACCs exhibited significantly lower levels of miR-139-3p (up to 8.49-fold, p<0.001), miR-675 (up to 23.25-fold, p<0.001) and miR-335 (up to 5.25-fold, p<0.001). A validation cohort of 16 specimen with known Weiss score showed up-regulation of miR-335 and miR-675 in the majority of cases with probable malignant course, although overlapping values exist.
  
  
  CONCLUSIONS
  miRNA profiling of miR-675 and miR-335 helps in discriminating ACCs from ACAs. miRNA analysis may indicate malignant behaviour in cases with indeterminate malignant potential.
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany. schmitzies@versanet.de
authors.forename: K J
authors.initials: KJ
authors.lastname: Schmitz
authors.forename: J
authors.initials: J
authors.lastname: Helwig
authors.forename: S
authors.initials: S
authors.lastname: Bertram
authors.forename: S Y
authors.initials: SY
authors.lastname: Sheu
authors.forename: A C
authors.initials: AC
authors.lastname: Suttorp
authors.forename: J
authors.initials: J
authors.lastname: Seggewiss
authors.forename: E
authors.initials: E
authors.lastname: Willscher
authors.forename: M K
authors.initials: MK
authors.lastname: Walz
authors.forename: K
authors.initials: K
authors.lastname: Worm
authors.forename: K W
authors.initials: KW
authors.lastname: Schmid
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics* / Q000378:metabolism; D018246:Adrenocortical Adenoma / Q000235:genetics* / Q000378:metabolism; D018268:Adrenocortical Carcinoma / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D003937:Diagnosis, Differential; D006801:Humans; D035683:MicroRNAs / Q000032:analysis / Q000096:biosynthesis*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; C555098:MIRN139 microRNA, human; C556347:MIRN335 microRNA, human; C548379:MIRN675 microRNA, human; D035683:MicroRNAs