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ERG rearrangement status and castration resistant prostate cancer: a prospective,population-based study
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
Dept. of Laboratory Medicine, University Hospital of Örebro, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.ORCID iD: 0000-0001-5533-7899
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Overtreatment is a major concern in prostate cancer (PCa) management, as no adequate prognostic tool exists to separate indolent from aggressive disease at time of diagnosis. Androgen deprivation therapy (ADT) is the standard treatment of locally recurrent or metastatic PCa and although most men respond well to ADT initially, inevitably a resistance to the treatment develops. Men with tumor growth despite the androgen-depleted environment are considered to have castration resistant PCa (CRPC). After developing CRPC, the median survival time is typically less than two years. Since the initial discovery of ERG rearrangement in PCa, several studies have investigated the association between ERG rearrangement and clinical outcome of PCa with discrepant results. Few studies have examined the association between ERG rearrangement and CRPC, despite the fact that the most common fusion partners to ERG are androgen regulated. In this study we investigated the association between ERG status and time to CRPC.

We assessed the ERG status in a cohort of 220 men initially managed by watchful waiting and treated with ADT at disease progression. There was no statistically significant association between ERG status and time from start of ADT to CPRC, or start of ADT to PCa-specific death. However, men harboring the ERG rearrangement did have a significantly shorter time between time of diagnosis and start of hormonal treatment, compared to men without the rearrangement (HR: 1.81; 95% CI: 1.23- 2.65), suggesting that ERG rearrangement is indicative of a more aggressive subtype of PCa./p>

National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-28474OAI: oai:DiVA.org:oru-28474DiVA, id: diva2:613039
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)
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Supervisors
Available from: 2013-03-26 Created: 2013-03-26 Last updated: 2019-03-01Bibliographically approved

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Carlsson, JessicaAndersson, Swen-OlofAndrén, Ove

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