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- 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.
- 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 castratetolerant 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.
- Subjects
CASTRATION; ANDROGENS; TESTOSTERONE; PROSTATE cancer; ADENOCARCINOMA; KAPLAN-Meier estimator
- Publication
BJU International, 2018, Vol 121, Issue 6, p971
- ISSN
1464-4096
- Publication type
Article
- DOI
10.1111/bju.14043