Fluorescence In situ Hybridization Analysis of Circulating Tumor Cells in Metastatic Prostate Cancer

Purpose:To assess the feasibility of characterizing gene copy number alteration by fluorescence in situ hybridization (FISH) of circulating tumor cells (CTC) isolated using the Cell Search system in patients with progressive castration-resistant metastatic prostate cancer. Experimental Design: We used probe combinations that included the androgen receptor (AR) and MYC genes for FISH analysis of CTC samples collected from 77 men with castration-resistant metastatic prostate cancer. Results: High-level chromosomal amplification of AR was detected in 38% and relative gain of MYC in 56% of samples analyzed. No such abnormalities were detected in samples with CTC counts of < 10, reflecting ascertainment difficulty in these lower count samples. Conclusion: The CTC isolated from our patient cohort present a very similar molecular cytogenetic profile to that reported for late-stage tumors and show that FISH analysis of CTC can be a valuable, noninvasive surrogate for routine tumor profiling. That as many as 50% of these patients have substantial amplification of the AR locus indicates that androgen signaling continues to play an important role in late-stage prostate cancer,