Prostate cancer patient-derived organoids: detailed outcome from a prospective cohort of 81 clinical specimens.

Servant, Raphaëlle; Garioni, Michele; Vlajnic, Tatjana; Blind, Melanie; Pueschel, Heike; Müller, David C; Zellweger, Tobias; Templeton, Arnoud J; Garofoli, Andrea; Maletti, Sina Laura; Piscuoglio, Salvatore; Rubin, Mark A.; Seifert, Helge; Rentsch, Cyrill A; Bubendorf, Lukas; Le Magnen, Clémentine (2021). Prostate cancer patient-derived organoids: detailed outcome from a prospective cohort of 81 clinical specimens. The journal of pathology, 254(5), pp. 543-555. Wiley 10.1002/path.5698

Preview

Text PATH-254-543.pdf - Published Version Available under License Creative Commons: Attribution-Noncommercial-No Derivative Works (CC-BY-NC-ND). Download (40MB) | Preview

Patient-derived organoids (PDOs) represent promising preclinical models in various tumor types. In the context of prostate cancer (PCa), however, their establishment has been hampered by poor success rates, which impedes their broad use for translational research applications. Along with the necessity to improve culture conditions, there is a need to identify factors influencing outcomes and to determine how to assess success versus failure in organoid generation. In the present study, we report our unbiased efforts to generate PDOs from a cohort of 81 PCa specimens with diverse pathological and clinical features. We comprehensively analyzed histological features of each enrolled sample (Gleason score, tumor content, proliferation index) and correlated them with organoid growth patterns. We identified improved culture conditions favoring the generation of PCa organoids, yet no specific intrinsic tumor feature was broadly associated with sustained organoid growth. In addition, we performed phenotypic and molecular characterization of tumor-organoid pairs using immunohistochemistry, immunofluorescence, fluorescence in situ hybridization, and targeted sequencing. Morphological and immunohistochemical profiles of whole organoids altogether provided a fast readout to identify the most promising ones. Notably, primary samples were associated with an initial take-rate of 83% (n = 60/72) in culture, with maintenance of cancer cells displaying common PCa alterations, such as PTEN loss and ERG overexpression. These cancer organoids were, however, progressively overgrown by organoids with a benign-like phenotype. Finally, out of nine metastasis samples, we generated a novel organoid model derived from a hormone-naïve lung metastasis, which displays alterations in the PI3K/Akt and Wnt/β-catenin pathways and responds to androgen deprivation. Taken together, our comprehensive study explores determinants of outcome and highlights the opportunities and challenges associated with the establishment of stable tumor organoid lines derived from PCa patients. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

Interest & Impact

Downloads

45 since deposited on 11 Jan 2022
15 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item