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Volume 67, Issue 3, Pages (March 2015)

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Presentation on theme: "Volume 67, Issue 3, Pages (March 2015)"— Presentation transcript:

1 Volume 67, Issue 3, Pages 496-503 (March 2015)
Patient-derived Xenografts Reveal that Intraductal Carcinoma of the Prostate Is a Prominent Pathology in BRCA2 Mutation Carriers with Prostate Cancer and Correlates with Poor Prognosis  Gail P. Risbridger, Renea A. Taylor, David Clouston, Ania Sliwinski, Heather Thorne, Sally Hunter, Jason Li, Gillian Mitchell, Declan Murphy, Mark Frydenberg, David Pook, John Pedersen, Roxanne Toivanen, Hong Wang, Melissa Papargiris, Mitchell G. Lawrence, Damien M. Bolton  European Urology  Volume 67, Issue 3, Pages (March 2015) DOI: /j.eururo Copyright © 2014 European Association of Urology Terms and Conditions

2 Fig. 1 Identification of intraductal carcinoma of the prostate (IDC-P) pathology in patient-derived xenografts (PDXs) and primary specimens from BRCA2 pathogenic mutation carriers. (A, B) PDX tumour showing prominent regions of IDC-P with solid or solid/cribriform architecture (haematoxylin and eosin), marked cytologic atypia, areas of central necrosis, and peripheral basal cells containing p63-positive basal cells and α-methylacyl-coenzyme A racemase (AMACR)–positive, ERG fusion–positive tumour cells. (C) Review of all BRCA2 and BRCAX (no BRCA1/BRCA2 mutation) cases used for PDX showed that the primary specimen contained AMACR/p63–positive IDC-P prior to PDX. Scale=250μm in (A) and (C), 50μm in (B). AMACR=α-methylacyl-coenzyme A racemase; CK8&18=cytokeratins 8/18; H&E=haematoxylin and eosin. European Urology  , DOI: ( /j.eururo ) Copyright © 2014 European Association of Urology Terms and Conditions

3 Fig. 2 Copy number analysis of intraductal carcinoma of the prostate (IDC-P) from a primary prostate cancer specimen matched to its patient-derived xenograft (PDX) from a BRCA2 mutation carrier. (A) Regions of copy number loss (red) and copy number gain (blue) occurring in each sample according to chromosome location in IDC-P from the primary specimen compared with IDC-P obtained from the matched PDX. The region or length of the chromosome that is altered is represented by the length of the bars. (B) Frequency plot of each copy number change (losses in red, gains in blue) per chromosome for primary and PDX IDC-P specimens in (A). When a change in copy number occurs in only one sample, it is displayed as a short single bar, whereas common changes are indicated by the increased amplitude in the bar. There was 83% similarity between the original tissue and PDX. ICD-P=intraductal carcinoma of the prostate; PDX=patient-derived xenograft. European Urology  , DOI: ( /j.eururo ) Copyright © 2014 European Association of Urology Terms and Conditions

4 Fig. 3 Fifteen-year Kaplan-Meier overall survival analysis of three BRCA groups. (A) Overall deaths in BRCA2 mutation carriers with intraductal carcinoma of the prostate (IDC-P) (blue line) compared with BRCA2 mutation carriers without IDC-P (orange line); age-adjusted hazard ratio [HR]: 16.9; p= (B) Overall deaths in patients with no BRCA1/BRCA2 mutation (BRCAX) with IDC-P (blue line) compared with BRCAX patients without IDC-P (orange line); age-adjusted HR: 3.57; p= (C) Overall deaths in BRCAX patients with IDC-P (blue line) compared with BRCA2 carriers with IDC-P (orange line); age-adjusted HR: 0.588; p=0.35. BRCAX=no BRCA1/BRCA2 mutation; IDC-P=intraductal carcinoma of the prostate. European Urology  , DOI: ( /j.eururo ) Copyright © 2014 European Association of Urology Terms and Conditions


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