Intraductal carcinoma of the prostate can evade androgen deprivation, with emergence of castrate-tolerant cells
AuthorPorter, LH; Hashimoto, K; Lawrence, MG; Pezaro, C; Clouston, D; Wang, H; Papargiris, M; Thorne, H; Li, J; Ryan, A; ...
Source TitleBJU International
University of Melbourne Author/sMoon, Daniel; Murphy, Declan; Risbridger, Gail; Li, Jason; Bolton, Damien; Sengupta, Shomik
AffiliationSir Peter MacCallum Department of Oncology
Surgery (Austin & Northern Health)
Surgery (St Vincent's)
Document TypeJournal Article
CitationsPorter, L. H., Hashimoto, K., Lawrence, M. G., Pezaro, C., Clouston, D., Wang, H., Papargiris, M., Thorne, H., Li, J., Ryan, A., Norden, S., Moon, D., Bolton, D. M., Sengupta, S., Frydenberg, M., Murphy, D. G., Risbridger, G. P. & Taylor, R. A. (2018). Intraductal carcinoma of the prostate can evade androgen deprivation, with emergence of castrate-tolerant cells. BJU INTERNATIONAL, 121 (6), pp.971-978. https://doi.org/10.1111/bju.14043.
Access StatusOpen Access
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.
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