title: Heterogeneous PSMA expression on circulating tumor cells: a potential basis for stratification and monitoring of PSMA-directed therapies in prostate cancer.
abstract: 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.
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Gorges
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Riethdorf
authors.affiliation: BPH-DD-TRG-CIPL-Biomarker Research, Bayer Pharma AG, Berlin, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: von Ahsen
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Paulina
authors.initials: P
authors.lastname: Nastał Y
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Röck
authors.affiliation: ATURO, Urology Practice, Berlin, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Boede
authors.affiliation: Department of Transfusion Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Peine
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Andra
authors.initials: A
authors.lastname: Kuske
authors.affiliation: BPH-DD-TRG-CIPL-Biomarker Research, Bayer Pharma AG, Berlin, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Schmid
authors.affiliation: BPH-DD-TRG-CIPL-Biomarker Research, Bayer Pharma AG, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kneip
authors.affiliation: ATURO, Urology Practice, Berlin, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: König
authors.affiliation: BPH-DD-TRG-CIPL-Biomarker Research, Bayer Pharma AG, Berlin, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Rudolph
authors.affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Pantel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D005434:Flow Cytometry / Q000379:methods; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating; D017430:Prostate-Specific Antigen / Q000032:analysis*; D011471:Prostatic Neoplasms / Q000175:diagnosis*
chemical_list: D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen
keywords: CellSearch®; PSMA; circulating tumor cells; prostate cancer