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

Abstract

Increased <i>AR</i> 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 <i>AR</i> gene is a common mechanism by which mCRPC increase <i>AR</i> activity. To determine whether <i>AR</i> 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 <i>AR</i> amplification status in CTCs and matched biopsy tissue from the same patient by fluorescence <i>in situ</i> hybridization (FISH). <i>AR</i> gene status in CTCs showed strong concordance with <i>AR</i> gene status in matched tissue samples in 24 of 25 patients (Correlation: 96%; Kappa: 0.83; Sensitivity: 100%, Specificity: 83%). Our work demonstrates that <i>AR</i> amplification is conserved between CTCs and biopsies and that CTCs can serve as non-invasive surrogate to document <i>AR</i> amplification in mCRPC.