Research Papers:

Androgen receptor amplification is concordant between circulating tumor cells and biopsies from men undergoing treatment for metastatic castration resistant prostate cancer

Jennifer Podolak, Kristi Eilers, Timothy Newby, Rachel Slottke, Erin Tucker, Susan B. Olson, Hui-Wen Lue, Jack Youngren, Rahul Aggarwal, Eric J. Small, Julie N. Graff, Joshi J. Alumkal, Tomasz M. Beer and George V. Thomas _

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Oncotarget. 2017; 8:71447-71455. https://doi.org/10.18632/oncotarget.16169

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Jennifer Podolak1, Kristi Eilers1, Timothy Newby1, Rachel Slottke1, Erin Tucker1, Susan B. Olson2, Hui-Wen Lue1, Jack Youngren3, Rahul Aggarwal3, Eric J. Small3, Julie N. Graff1, Joshi J. Alumkal1, Tomasz M. Beer1 and George V. Thomas1,2

1Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA

2Department of Pathology and Laboratory Medicine, Oregon Health and Science University, Portland, OR, USA

3School of Medicine, University of California, San Francisco, CA, USA

Correspondence to:

George V. Thomas, email: [email protected]

Keywords: prostate cancer, circulating tumor cells, androgen receptor, metastases, metastatic castration resistant prostate cancer

Received: September 30, 2016     Accepted: February 27, 2017     Published: March 13, 2017


Increased AR activity has been shown to be preserved in spatially distinct metastatic tumors from the same patient suggesting the requirement for lineage-specific dependencies for metastatic castration resistant prostate cancer (mCRPC). Amplification of the AR gene is a common mechanism by which mCRPC increase AR activity. To determine whether AR amplification in circulating tumor cells (CTC) could complement metastatic tissue biopsies in men undergoing treatment for mCRPC, we developed a novel two-step assay to isolate CTCs and subsequently analyzed AR amplification status in CTCs and matched biopsy tissue from the same patient by fluorescence in situ hybridization (FISH). AR gene status in CTCs showed strong concordance with AR gene status in matched tissue samples in 24 of 25 patients (Correlation: 96%; Kappa: 0.83; Sensitivity: 100%, Specificity: 83%). Our work demonstrates that AR amplification is conserved between CTCs and biopsies and that CTCs can serve as non-invasive surrogate to document AR amplification in mCRPC.

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