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A comparative study of ERG status assessment on DNA-, mRNA-, and proteinlevels using unique samples from a Swedish biopsy cohort
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Dept. of Prostate Cancer Research, Institute of Pathology, University Hospital of Bonn, Bonn, Germany.
Dept. of Urology, University Hospital of Örebro, Sweden; Dept. of Laboratory Medicine, University Hospital of Örebro, Sweden.
Hologic Gen-Probe, San Diego, USA.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

The ERG rearrangement is identified in approximately 50% of prostate cancer (PCa) screened cohorts and is known to be highly specific. This genetic aberration, most commonly leading to the TMPRSS2-ERG fusion, but also SLC45A3-ERG or NDRG1- ERG fusions, all leading to an over expression of a truncated ERG protein. Most studies have applied in situ hybridization (FISH) methods or mRNA based assays to investigate the ERG status. Recently, studies showed that ERG protein levels assessed by ERG antibodies can be used as a surrogate marker for ERG rearrangement. In the current study we investigate ERG status on a series of diagnostic biopsies using DNA-, mRNA- and protein based assays. We formally compare three assay results (i.e. FISH, fusion mRNA and immunohistochemistry) to identify which method could be most appropriate to use when having limited amount of tissue. ERG rearrangement was found in 56% of the cases. Comparing ERG rearrangement status by FISH with ERG over expression and TMPRSS2-ERG fusion transcript we found 95.1% (154/162, Fisher’s exact test 9.50E-36) and 85.2% (138/162, Fisher’s exact test 7.26E-22) concordance, respectively. We show that the ERG antibody highly correlates with the ERG rearrangement with high sensitivity and specificity. We also identified the most common TMPRSS2-ERG isoform in the majority of ERG rearranged cases. These results provide compelling evidence that the ERG antibody can be used to further investigate the role of ERG in PCa.

Keywords [en]
Prostate cancer, ERG rearrangement, Fluorescence in situ hybridization, Immunohistochemistry
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-28475OAI: oai:DiVA.org:oru-28475DiVA, id: diva2:613047
Available from: 2013-03-26 Created: 2013-03-26 Last updated: 2017-10-17Bibliographically approved
In thesis
1. Assessing the ERG rearrangement for clinincal use in patients with prostrate cancer
Open this publication in new window or tab >>Assessing the ERG rearrangement for clinincal use in patients with prostrate cancer
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In Sweden, close to 10 000 men are annually diagnosed with prostate cancer (PCa) and approximately 2400 men die of their disease each year. Today there is no reliable marker that can separate patients who will have an aggressive type of disease that requires treatment, from patients who will have a more indolent clinical course and can be left untreated. This further leads to the current problem of over treatment of men with PCa. Hence, there is an urgent need for reliable prognostic markers that can be used at time of diagnosis. With the discovery of recurrent gene rearrangements in PCa, most commonly ERG rearrangements, hope came that this aberration could play a role in diagnosis and/or prognosis of the disease.

The aim of this thesis was to investigate the clinical implication of ERG rearrangements in the management of PCa.

The work in this thesis supports the findings from previous studies, suggesting that the ERG rearrangement is a sign of a more aggressive type of cancer. The major findings are that in multifocal PCa, the ERG rearranged cancer foci are more prone to metastatic dissemination compared to foci without the ERG rearrangement and that patients harboring the ERG rearrangement have a faster disease progression leading up to earlier start of hormonal treatment. Furthermore, the results add an additional level of complexity in a subset of PCa tumors that harbor multiple gene rearrangements on the cellular level. The result also show that the newly available ERG antibody is highly predictive of ERG rearrangement and is appropriate to use when faced with limitations in tissue amounts.

The findings in this thesis indicate that the ERG rearrangement has a potential role in the clinical management of PCa but further studies arerequired.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2013. p. 65
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 82
Keywords
Prostate cancer, prognosis, biomarkers, ETS genes, ERG rearrangement, fluoroscence in situ hybridization
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-28471 (URN)978-91-7668-918-9 (ISBN)
Public defence
2013-04-26, Wilandersalen, Universitetssjukhuset, Grev Rosengatan 18, 703 62 Örebro, 09:31 (Swedish)
Opponent
Supervisors
Available from: 2013-03-26 Created: 2013-03-26 Last updated: 2019-03-01Bibliographically approved

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Helenius, GiselaAndersson, Swen-OlofAndrén, Ove

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School of Health and Medical Sciences, Örebro University, SwedenSchool of Medicine, Örebro University, Sweden
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