Intraductal carcinoma of the prostate can evade androgen deprivation, with emergence of castrate-tolerant cells
© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd..
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.
| Errataetall: |
CommentIn: Nat Rev Urol. 2017 Oct 31;14(11):641. - PMID 29086762 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:121 |
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| Enthalten in: |
BJU international - 121(2018), 6 vom: 13. Juni, Seite 971-978 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Porter, Laura H [VerfasserIn] |
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| Links: |
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| Themen: |
#PCSM |
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| Anmerkungen: |
Date Completed 28.01.2019 Date Revised 28.01.2019 published: Print-Electronic CommentIn: Nat Rev Urol. 2017 Oct 31;14(11):641. - PMID 29086762 Citation Status MEDLINE |
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| doi: |
10.1111/bju.14043 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM276472683 |
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| 100 | 1 | |a Porter, Laura H |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Intraductal carcinoma of the prostate can evade androgen deprivation, with emergence of castrate-tolerant cells |
| 264 | 1 | |c 2018 | |
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| 500 | |a Date Completed 28.01.2019 | ||
| 500 | |a Date Revised 28.01.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Nat Rev Urol. 2017 Oct 31;14(11):641. - PMID 29086762 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd. | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a #ProstateCancer | |
| 650 | 4 | |a androgen deprivation therapy | |
| 650 | 4 | |a intraductal carcinoma of the prostate | |
| 650 | 4 | |a pathology | |
| 650 | 4 | |a patient-derived xenografts | |
| 650 | 7 | |a Androgen Antagonists |2 NLM | |
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