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ERG Rearrangement Metastasis Patterns in Locally Advanced Prostate Cancer
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
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2010 (English)In: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 75, no 4, p. 762-767Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES To interrogate multifocal prostate cancer (PCa) to determine its predilection for metastasis, using ERG rearrangement as marker of clonality. A hallmark of PCa is that distinct tumor foci may arise independently, which has important biological and clinical implications. Recent studies characterizing ERG-rearranged PCa possessing intrafocal homogeneity but interfocal heterogeneity support this hypothesis. METHODS We studied 26 patients who underwent prostatectomy and lymphadenectomy with at least 2 distinct PCa foci and 1 lymph node (LN) metastasis. Each focus was assessed for size, Gleason score, ERG rearrangement, and TMPRSS2-ERG transcript. RESULTS Fifteen of 26 cases exhibited interfocal homogeneity with regard to ERG rearrangement (ie, presence vs absence of ERG rearrangement). ERG rearrangement was present in all foci for 6 and absent in all foci for 9 cases. Two cases revealed interfocal heterogeneity with regard to rearrangement mechanism ( ie, rearrangement through insertion or deletion). Eight of 26 cases revealed interfocal heterogeneity with regard to rearrangement status. In all cases with at least 1 ERG rearranged focus, we found the corresponding LN metastasis harboring an ERG rearrangement. Interestingly, in a subset of cases the rearrangement status in the LN did not correspond to size or Gleason score. All but 2 ERG rearranged foci had detectable TMPRSS2-ERG transcript levels. CONCLUSIONS When multifocal PCa demonstrates both ERG-positive and ERG-negative foci, the positive foci have a greater predilection for metastasis. Larger studies are needed to confirm the potential additional risk an ERG rearranged focus confers on the likelihood of disease progression. UROLOGY 75: 762-767, 2010. (C) 2010 Elsevier Inc.

Place, publisher, year, edition, pages
2010. Vol. 75, no 4, p. 762-767
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-28473DOI: 10.1016/j.urology.2009.10.010ISI: 000276258300002OAI: oai:DiVA.org:oru-28473DiVA, id: diva2:613030
Available from: 2013-03-26 Created: 2013-03-26 Last updated: 2018-04-24Bibliographically 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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Available from: 2013-03-26 Created: 2013-03-26 Last updated: 2019-03-01Bibliographically approved

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