Laura H Porter1,2, Kohei Hashimoto1,3, Mitchell G Lawrence1,2, Carmel Pezaro1,4, David Clouston5, Hong Wang1, Melissa Papargiris1,6, Heather Thorne7,8, Jason Li9, Andrew Ryan5, Sam Norden5, Daniel Moon10,11, Damien M Bolton12,13, Shomik Sengupta12,13, Mark Frydenberg1,14, Declan G Murphy8,15, Gail P Risbridger1,2, Renea A Taylor1,16. 1. Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, Vic., Australia. 2. Prostate Cancer Research Program, Cancer Research Division, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Vic., Australia. 3. Department of Urology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan. 4. Eastern Health Clinical School, Monash University, Melbourne, Vic., Australia. 5. TissuPath, Mount Waverley, Vic., Australia. 6. Australian Prostate Cancer Bioresource, Victorian Node, Monash University, Melbourne, Vic., Australia. 7. kConFab, Research Department, Peter MacCallum Cancer Centre, Melbourne, Vic., Australia. 8. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Vic., Australia. 9. Bioinformatics Core, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Vic., Australia. 10. Epworth Healthcare, Richmond, Vic., Australia. 11. Central Clinical School, Monash University, Melbourne, Vic., Australia. 12. Department of Urology, Austin Hospital, Melbourne, Heidelberg, Vic., Australia. 13. Department of Surgery, University of Melbourne, Melbourne, Vic., Australia. 14. Department of Surgery, Monash University, Melbourne, Vic., Australia. 15. Division of Cancer Surgery, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Vic., Australia. 16. Department of Physiology, Biomedicine Discovery Institute, Cancer Program, Monash University, Melbourne, Vic., Australia.
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.
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.
Authors: Gail P Risbridger; Ashlee K Clark; Laura H Porter; Mitchell G Lawrence; Renea A Taylor; Roxanne Toivanen; Andrew Bakshi; Natalie L Lister; David Pook; Carmel J Pezaro; Shahneen Sandhu; Shivakumar Keerthikumar; Rosalia Quezada Urban; Melissa Papargiris; Jenna Kraska; Heather B Madsen; Hong Wang; Michelle G Richards; Birunthi Niranjan; Samantha O'Dea; Linda Teng; William Wheelahan; Zhuoer Li; Nicholas Choo; John F Ouyang; Heather Thorne; Lisa Devereux; Rodney J Hicks; Shomik Sengupta; Laurence Harewood; Mahesh Iddawala; Arun A Azad; Jeremy Goad; Jeremy Grummet; John Kourambas; Edmond M Kwan; Daniel Moon; Declan G Murphy; John Pedersen; David Clouston; Sam Norden; Andrew Ryan; Luc Furic; David L Goode; Mark Frydenberg Journal: Nat Commun Date: 2021-08-19 Impact factor: 14.919
Authors: Mitchell G Lawrence; Daisuke Obinata; Shahneen Sandhu; Luke A Selth; Stephen Q Wong; Laura H Porter; Natalie Lister; David Pook; Carmel J Pezaro; David L Goode; Richard J Rebello; Ashlee K Clark; Melissa Papargiris; Jenna Van Gramberg; Adrienne R Hanson; Patricia Banks; Hong Wang; Birunthi Niranjan; Shivakumar Keerthikumar; Shelley Hedwards; Alisee Huglo; Rendong Yang; Christine Henzler; Yingming Li; Fernando Lopez-Campos; Elena Castro; Roxanne Toivanen; Arun Azad; Damien Bolton; Jeremy Goad; Jeremy Grummet; Laurence Harewood; John Kourambas; Nathan Lawrentschuk; Daniel Moon; Declan G Murphy; Shomik Sengupta; Ross Snow; Heather Thorne; Catherine Mitchell; John Pedersen; David Clouston; Sam Norden; Andrew Ryan; Scott M Dehm; Wayne D Tilley; Richard B Pearson; Ross D Hannan; Mark Frydenberg; Luc Furic; Renea A Taylor; Gail P Risbridger Journal: Eur Urol Date: 2018-07-23 Impact factor: 20.096