Please use this identifier to cite or link to this item: http://hdl.handle.net/11434/1263
Title: Intraductal carcinoma of the prostate can evade androgen deprivation, with emergence of castrate-tolerant cells.
Epworth Authors: Moon, Daniel
Other Authors: Porter, Laura
Hashimoto, Kohei
Lawrence, Mitchell
Pezaro, Carmel
Clouston, David
Wang, Hong
Papargiris, Melissa
Thorne, Heather
Li, Jason
KConFab
Ryan, Andrew
Norden, Sam
Bolton, Damien
Sengupta, Shomik
Frydenberg, Mark
Murphy, Declan
Risbridger, Gail
Taylor, Renea
Keywords: Pathology
Androgen Deprivation Therapy
ADT
Intraductal Carcinoma of the Prostate
IDC-P
BRCA Mutations
Prostate Cancer
Patient-Derived Xenografts
PDXs
Castration
Biopsy
Castrate-Tolerant Cells
Survival
Adenocarcinoma
Tumour Regeneration
Kaplan–Meier
Advanced Prostate Cancer
Testosterone Restoration
UroRenal, Vascular Clinical Institute, Epworth HealthCare, Victoria, Australia
Australian Prostate Cancer Research Centre Epworth HealthCare, Victoria, Australia
Issue Date: Oct-2017
Publisher: Wiley Online Library
Citation: BJU Int. 2017 Oct 4
Abstract: OBJECTIVE: 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). MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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://hdl.handle.net/11434/1263
DOI: 10.1111/bju.14043
PubMed URL: https://www.ncbi.nlm.nih.gov/pubmed/28977728
ISSN: 1464-410X
Journal Title: BJU International
Type: Journal Article
Affiliated Organisations: Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, Vic., Australia.
Prostate Cancer Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Vic., Australia.
Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan.
Eastern Health Clinical School, Monash University, Melbourne, Vic., Australia.
Australian Prostate Cancer Bioresource, Victorian Node, Monash University, Melbourne, Vic., Australia.
kConFab, Research Department, Peter MacCallum Cancer Centre, Melbourne, Vic., Australia.
Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Vic., Australia.
Bioinformatics Core, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Vic., Australia.
Central Clinical School, Monash University, Melbourne, Vic., Australia.
Department of Urology, Austin Hospital, Melbourne, Heidelberg, Vic., Australia.
Department of Surgery, University of Melbourne, Melbourne, Vic., Australia.
Department of Surgery, Monash University, Melbourne, Vic., Australia.
Division of Cancer Surgery, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Vic., Australia.
Department of Physiology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, Vic., Australia.
Type of Clinical Study or Trial: Retrospective studies
Appears in Collections:Cancer Services
Epworth Prostate Centre
Epworth Prostate Centre

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