Differential expression of microRNA-675, microRNA-139-3p and microRNA-335 in benign and malignant adrenocortical tumours
- K J Schmitz1,2,
- J Helwig1,
- S Bertram1,
- S Y Sheu1,
- A C Suttorp1,
- J Seggewiß3,
- E Willscher3,
- M K Walz4,
- K Worm1,
- K W Schmid1
- 1Institute of Pathology and Neuropathology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
- 2Pathologisches Institut Recklinghausen, Recklinhausen, Germany
- 3Integrated Functional Genomics (IFG), Interdisciplinary Center for Clinical Research (IZKF), University Hospital of Muenster, Westfalian Wilhelms-University of Muenster, Muenster, Germany
- 4Department of Surgery and Centre of Minimally Invasive Surgery, Kliniken Essen-Mitte, Essen, Germany
- Correspondence to Klaus J Schmitz, Institute of Pathology and Neuropathology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, Essen 45122, Germany;
- Accepted 9 March 2011
- Published Online First 6 April 2011
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.
Conclusion 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.
Funding This work has been supported by the local research fund (IFORES) of the University of Essen.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
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