Heterogeneous PSMA expression on circulating tumor cells - a potential basis for stratification and monitoring of PSMA-directed therapies in prostate cancer
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Tobias M. Gorges1,*, Sabine Riethdorf1,*, Oliver von Ahsen2,*, Paulina Nastały1, Katharina Röck1, Marcel Boede3, Sven Peine4, Andra Kuske1, Elke Schmid2, Christoph Kneip2, Frank König3, Marion Rudolph2, Klaus Pantel1
1Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
2BPH-DD-TRG-CIPL-Biomarker Research, Bayer Pharma AG, Berlin, Germany
3ATURO, Urology Practice, Berlin, Germany
4Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
*Shared first authorship
Klaus Pantel, e-mail: [email protected]
Keywords: CellSearch®, circulating tumor cells, prostate cancer, PSMA
Received: January 29, 2016 Accepted: April 16, 2016 Published: April 26, 2016
The prostate specific membrane antigen (PSMA) is the only clinically validated marker for therapeutic decisions in prostate cancer (PC). Characterization of circulating tumor cells (CTCs) obtained from the peripheral blood of PC patients might provide an alternative to tissue biopsies called “liquid biopsy”. The aim of this study was to develop a reliable assay for the determination of PSMA on CTCs. PSMA expression was analyzed on tissue samples (cohort one, n = 75) and CTCs from metastatic PC patients (cohort two, n = 29). Specific signals for the expression of PSMA could be seen for different prostate cancer cell line cells (PC3, LaPC4, 22Rv1, and LNCaP) by Western blot, immunohistochemistry (IHC), immunocytochemistry (ICC), and FACS. PSMA expression was found to be significantly increased in patients with higher Gleason grade (p = 0.0011) and metastases in lymph nodes (p = 0.0000085) or bone (p = 0.0020) (cohort one). In cohort two, CTCs were detectable in 20 out of 29 samples (69 %, range from 1 - 1000 cells). Twelve out of 20 CTC-positive patients showed PSMA-positive CTCs (67 %, score 1+ to 3+). We found intra-patient heterogeneity regarding the PSMA status between CTCs and the corresponding primary tumors. The results of our study could help to address the question whether treatment decisions based on CTC PSMA profiling will lead to a measurable benefit in clinical outcome for prostate cancer patients in the near future.
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