Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/18412
Title: Intraductal carcinoma of the prostate can evade androgen deprivation, with emergence of castrate-tolerant cells.
Authors: Porter, Laura H;Hashimoto, Kohei;Lawrence, Mitchell G;Pezaro, Carmel;Clouston, David;Wang, Hong;Papargiris, Melissa;Thorne, Heather;Li, Jason;Ryan, Andrew;Norden, Sam;Moon, Daniel;Bolton, Damien M;Sengupta, Shomik;Frydenberg, Mark;Murphy, Declan G;Risbridger, Gail P;Taylor, Renea A
Affiliation: Epworth Healthcare, Richmond, Vic., Australia
Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, Vic., Australia
Department of Surgery, University of Melbourne, Melbourne, Vic., Australia
Department of Urology, Austin Health, Heidelberg, Victoria, Australia
Central Clinical School, Monash University, Melbourne, Vic., Australia
Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan
Eastern Health Clinical School, Monash University, Melbourne, Vic., Australia
Prostate Cancer Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Vic., Australia
Australian Prostate Cancer Bioresource, Victorian Node, Monash University, Melbourne, Vic., Australia
Bioinformatics Core, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Vic., Australia
kConFab, Research Department, Peter MacCallum Cancer Centre, Melbourne, Vic., Australia
TissuPath, Mount Waverley, Vic., Australia
Department of Surgery, Monash University, Melbourne, Vic., Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Vic., Australia
Department of Physiology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, Vic., Australia
Division of Cancer Surgery, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Vic., Australia
Issue Date: Jun-2018
EDate: 2017-10-26
Citation: BJU international 2018; 121(6): 971-978
Abstract: To determine the relevance of intraductal carcinoma of the prostate (IDC-P) in advanced prostate cancer by first examining whether IDC-P was originally present in patients who later developed advanced prostate cancer and then using patient-derived xenografts (PDXs) to investigate the response of IDC-P to androgen deprivation therapy (ADT). We conducted a retrospective pathology review of IDC-P in primary prostate biopsy or surgery specimens from 38 men who subsequently developed advanced prostate cancer. Overall survival was calculated using the Kaplan-Meier method. To demonstrate the response of IDC-P to ADT, we established PDXs from seven patients with familial and/or high-risk sporadic prostate cancer. After castration and testosterone restoration of host mice, we measured the volume and proliferation of IDC-P within PDX grafts. We found that IDC-P was a prominent feature in the primary prostate specimens, present in 63% of specimens and often co-existing with poorly differentiated adenocarcinoma. Overall survival was similar in patients with or without IDC-P. In the PDXs from all seven patients, IDC-P was identified and present at a similar volume to adenocarcinoma. Residual IDC-P lesions persisted after host castration and, similar to castrate-tolerant adenocarcinoma, testosterone restoration led to tumour regeneration. The study showed that IDC-P is prevalent in aggressive prostate cancer and contains cells that can withstand androgen deprivation. Thus, IDC-P appears functionally relevant in advanced prostate cancer. The presence of IDC-P may be a trigger to develop innovative clinical management plans.
URI: http://ahro.austin.org.au/austinjspui/handle/1/18412
DOI: 10.1111/bju.14043
ORCID: 0000-0002-1557-2584
0000-0002-5145-6783
0000-0003-3357-1216
0000-0002-7500-5899
0000-0003-2609-2380
PubMed URL: 28977728
Type: Journal Article
Subjects: BRCA
#PCSM
#ProstateCancer
androgen deprivation therapy
intraductal carcinoma of the prostate
pathology
patient-derived xenografts
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.