McDaniel, A. S., Ferraldeschi, R., Krupa, R., Landers, M., Graf, R., Louw, J., Jendrisak, A., Bales, N., Marrinucci, D., Zafeiriou, Z., Flohr, P., Sideris, S., Crespo, M., Figueiredo, I., Mateo, J., de Bono, J. S., Dittamore, R., Tomlins, S. A., Attard, G. (2017) Phenotypic diversity of circulating tumour cells in patients with metastatic castration-resistant prostate cancer. BJU INTERNATIONAL, 120 (5B). E30-E44. ISSN 1464-4096

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Abstract

Objectives To use a non-biased assay for circulating tumour cells (CTCs) in patients with prostate cancer (PCa) in order to identify non-traditional CTC phenotypes potentially excluded by conventional detection methods that are reliant on antigen- and/or size-based enrichment. Patients and Methods A total of 41 patients with metastatic castration-resistant PCa (mCRPC) and 20 healthy volunteers were analysed on the Epic CTC platform, via high-throughput imaging of DAPI expression and CD45/cytokeratin (CK) immunofluorescence (IF) on all circulating nucleated cells plated on glass slides. To confirm the PCa origin of CTCs, IF was used for androgen receptor (AR) expression and fluorescence in situ hybridization was used for PTEN and ERG assessment. Results Traditional CTCs (CD45(-)/CK+/morphologically distinct) were identified in all patients with mCRPC and we also identified CTC clusters and non-traditional CTCs in patients with mCRPC, including CK- and apoptotic CTCs. Small CTCs (<= white blood cell size) were identified in 98% of patients with mCRPC. Total, traditional and non-traditional CTCs were significantly increased in patients who were deceased vs alive after 18 months; however, only non-traditional CTCs were associated with overall survival. Traditional and total CTC counts according to the Epic platform in the mCRPC cohort were also significantly correlated with CTC counts according to the CellSearch system. Conclusions Heterogeneous non-traditional CTC populations are frequent in mCRPC and may provide additional prognostic or predictive information.

Item Type:	Article
Authors (ICR Faculty only):	Attard, Gert and De Bono, Johann
All Authors:	McDaniel, A. S., Ferraldeschi, R., Krupa, R., Landers, M., Graf, R., Louw, J., Jendrisak, A., Bales, N., Marrinucci, D., Zafeiriou, Z., Flohr, P., Sideris, S., Crespo, M., Figueiredo, I., Mateo, J., de Bono, J. S., Dittamore, R., Tomlins, S. A., Attard, G.
Additional Information:	ISI Document Delivery No.: FR9ZM Times Cited: 1 Cited Reference Count: 39 McDaniel, Andrew S. Ferraldeschi, Roberta Krupa, Rachel Landers, Mark Graf, Ryon Louw, Jessica Jendrisak, Adam Bales, Natalee Marrinucci, Dena Zafeiriou, Zafeiris Flohr, Penelope Sideris, Spyridon Crespo, Mateus Figueiredo, Ines Mateo, Joaquin de Bono, Johann S. Dittamore, Ryan Tomlins, Scott A. Attard, Gerhardt Movember GAP CTC programme; National Institute for Health Research; National Institutes of Health [R01 CA183857] This work was in-part supported by funding from the Movember GAP CTC programme, National Institute for Health Research to The Royal Marsden/Institute of Cancer Research Biomedical Research Centre and National Institutes of Health (R01 CA183857 to S.A.T.). G.A. is a Cancer Research UK clinician scientist. We thank the participating men and their families who had metastatic PCa and nonetheless gave the gift of participation so that others might benefit. 1 0 Wiley Hoboken 1464-410x Si
Uncontrolled Keywords:	circulating tumour cells liquid biopsy metastatic castration-resistant prostate cancer ERG PTEN epithelial-mesenchymal transition breast-cancer lethal expression biomarkers markers blood erg Urology & Nephrology
Research teams:	ICR divisions > Cancer Therapeutics > Cancer Biomarkers ICR divisions > Clinical Studies > Cancer Biomarkers Clinical Units > Urology Unit ICR divisions > Clinical Studies > Prostate Cancer Targeted Therapy Group ICR divisions > Molecular Pathology > Treatment Resistance
Depositing User:	Barry Jenkins
Date Deposited:	18 Jan 2018 10:33
Last Modified:	18 Jan 2018 10:33
URI:	http://publications.icr.ac.uk/id/eprint/16528

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