Platinum Priority – Prostate Cancer Editorial by XXX on pp. x–y of this issue A Prostate Cancer ‘‘Nimbosus’’: Genomic Instability and SChLAP1 Dysregulation Underpin Aggression of Intraductal and Cribriform Subpathologies Melvin L.K. Chua a,y , Winnie Lo a , Melania Pintilie a , Jure Murgic a,z , Emilie Lalonde b,c , Vinayak Bhandari b,c , Osman Mahamud c , Anuradha Gopalan d , Charlotte F. Kweldam e , Geert J.L.H. van Leenders e , Esther I. Verhoef e , Agnes Marije Hoogland e , Julie Livingstone b , Alejandro Berlin a , Alan Dal Pra a,§ , Alice Meng a , Junyan Zhang a , Miche `le Orain f , Vale ´rie Picard f , He ´le `ne Hovington f , Alain Bergeron f , Louis Lacombe f , Yves Fradet f , Bernard Teˆtu f , Victor E. Reuter d , Neil Fleshner g , Michael Fraser a , Paul C. Boutros b,c,h , Theodorus H. van der Kwast e,i,||, *, Robert G. Bristow a,c,||, ** a Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada; b Informatics and Biocomputing Program, Ontario Institute for Cancer Research, Toronto, ON, Canada; c Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada; d Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA; e Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands; f Centre de Recherche du CHU de Que ´bec-Universite ´ Laval, Que ´bec City, QC, Canada; g Division of Urology, University Health Network, University of Toronto, Toronto, ON, Canada; h Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada; i Laboratory Medicine Program, University Health Network, University of Toronto, Toronto, ON, Canada E U R O P E A N U R O L O G Y X X X ( 2 0 1 7 ) X X X – X X X ava ilable at www.sciencedirect.com journa l homepage: www.europea nurology.com Article info Article history: Accepted April 27, 2017 Associate Editor: Stephen Boorjian Keywords: Intraductal carcinoma Cribriform architecture Abstract Background: Intraductal carcinoma (IDC) and cribriform architecture (CA) represent unfavorable subpathologies in localized prostate cancer. We recently showed that IDC shares a clonal ancestry with the adjacent glandular adenocarcinoma. Objective: We investigated for the co-occurrence of ‘‘aggression’’ factors, genomic instability and hypoxia, and performed gene expression profiling of these tumors. Design, setting, and participants: A total of 1325 men were treated for localized prostate cancer from four academic institutions (University Health Network, CHU de Que ´ bec- Universite ´ Laval, Memorial Sloan Kettering Cancer Center [MSKCC], and Erasmus Medical Center). Pathological specimens were centrally reviewed. Gene copy number and expression, and intraprostatic oxygenation were assessed. y Current address: Division of Radiation Oncology, National Cancer Centre Singapore, Singapore. z Current address: Department of Oncology and Nuclear Medicine, University Hospital Center Sisters of Charity Zagreb School of Medicine, Zagreb, Croatia. § Current address: Department of Radiation Oncology, Bern University Hospital, Bern, Switzerland. || These authors shared co-senior authorship. * Corresponding author. Department of Pathology, Laboratory Medicine Program, Toronto General Hospital, 200 Elizabeth St, Toronto, ON, M5G 2C4, Canada. Tel. +1 416 340 4597. E-mail address: Theodorus.vanderKwast@uhn.ca (T.H. van der Kwast). ** Corresponding author. Radiation Medicine Program, Princess Margaret Cancer Centre and Depart- ments of Medical Biophysics and Radiation Oncology, University of Toronto, 610 University Ave, Toronto, ON, M5G 2M9, Canada. Tel. +1 416 946 2936; Fax: +1 416 946 4442. E-mail address: Rob.Bristow@rmp.uhn.on.ca (R.G. Bristow). EURURO-7365; No. of Pages 10 Please cite this article in press as: Chua MLK, et al. A Prostate Cancer ‘‘Nimbosus’’: Genomic Instability and SChLAP1 Dysregulation Underpin Aggression of Intraductal and Cribriform Subpathologies. Eur Urol (2017), http://dx.doi.org/10.1016/j.eur- uro.2017.04.034 http://dx.doi.org/10.1016/j.eururo.2017.04.034 0302-2838/# 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.