title: Cancer Prognosis Defined by the Combined Analysis of 8q, PTEN and ERG.
abstract: Overtreatment is a major concern in men diagnosed with prostate cancer. The aim of this study was to evaluate the combined prognostic role of three frequent molecular alterations in prostate cancer, namely relative 8q gain, ERG overexpression, and loss of PTEN expression, in a series of 136 patients with prostate cancer treated with prostatectomy and with a long follow-up. Fluorescent in situ hybridization was used to detect the relative copy number of 8q and immunohistochemistry was used for quantitative assessment of ERG and PTEN expression. During a median follow-up period of 117.8 months, 66 (49%) patients had disease recurrence. Relative 8q gain, ERG overexpression, and loss of PTEN expression were observed in 18%, 56%, and 33% of the cases, respectively. No association with patient recurrence-free survival was found for relative 8q gain or ERG overexpression on their own, whereas loss of PTEN expression was associated with worse recurrence-free survival (P=.006). Interestingly, in the subgroup of patients with normal PTEN expression, we found that the combined relative 8q gain/ERG overexpression is associated with high risk of recurrence (P=.008), suggesting that alternative mechanisms exist for progression into clinically aggressive disease. Additionally, in intermediate-risk patients with normal PTEN expression in their tumors, the combination of 8q gain/ERG overexpression was associated with a poor recurrence-free survival (P<.001), thus indicating independent prognostic value. This study shows that the combined analysis of 8q, ERG and PTEN contributes to an improved clinical outcome stratification of prostate cancer patients treated with radical prostatectomy.
authors.affiliation: Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal; Cancer Genetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal.
authors.forename: Maria P
authors.initials: MP
authors.lastname: Silva
authors.affiliation: Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal; Cancer Genetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal.
authors.forename: João D
authors.initials: JD
authors.lastname: Barros-Silva
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway; Center for Cancer Biomedicine, University of Oslo, Oslo, Norway.
authors.forename: Elin
authors.initials: E
authors.lastname: Ersvær
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway; Center for Cancer Biomedicine, University of Oslo, Oslo, Norway.
authors.forename: Wanja
authors.initials: W
authors.lastname: Kildal
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway; Center for Cancer Biomedicine, University of Oslo, Oslo, Norway; Department of Informatics, University of Oslo, 0310 Oslo, Norway.
authors.forename: Tarjei Sveinsgjerd
authors.initials: TS
authors.lastname: Hveem
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway; Center for Cancer Biomedicine, University of Oslo, Oslo, Norway.
authors.forename: Manohar
authors.initials: M
authors.lastname: Pradhan
authors.affiliation: Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Vieira
authors.affiliation: Department of Genetics, Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal; Cancer Genetics Group, IPO Porto Research Center (CI-IPOP), Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal; Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal. Electronic address: manuel.teixeira@ipoporto.min-saude.pt.
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
authors.affiliation: Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway; Center for Cancer Biomedicine, University of Oslo, Oslo, Norway; Department of Informatics, University of Oslo, 0310 Oslo, Norway; Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford, United Kingdom. Electronic address: hdaniels@ifi.uio.no.
authors.forename: Håvard E
authors.initials: HE
authors.lastname: Danielsen