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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Heterogeneous PSMA expression on circulating tumor cells - a potential basis for stratification and monitoring of PSMA-directed therapies in prostate cancer. / Gorges, Tobias M; Riethdorf, Sabine; von Ahsen, Oliver; Nastały, Paulina; Röck, Katharina; Boede, Marcel; Peine, Sven; Kuske, Andra; Schmid, Elke; Kneip, Christoph; König, Frank; Rudolph, Marion; Pantel, Klaus.

In: ONCOTARGET, Vol. 7, No. 23, 07.06.2016, p. 34930-41.

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@article{f1e047fda1a340448b187ac7bb15ff39,
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.",
author = "Gorges, {Tobias M} and Sabine Riethdorf and {von Ahsen}, Oliver and Paulina Nasta{\l}y and Katharina R{\"o}ck and Marcel Boede and Sven Peine and Andra Kuske and Elke Schmid and Christoph Kneip and Frank K{\"o}nig and Marion Rudolph and Klaus Pantel",
year = "2016",
month = jun,
day = "7",
doi = "10.18632/oncotarget.9004",
language = "English",
volume = "7",
pages = "34930--41",
journal = "ONCOTARGET",
issn = "1949-2553",
publisher = "IMPACT JOURNALS LLC",
number = "23",

}

RIS

TY - JOUR

T1 - Heterogeneous PSMA expression on circulating tumor cells - a potential basis for stratification and monitoring of PSMA-directed therapies in prostate cancer

AU - Gorges, Tobias M

AU - Riethdorf, Sabine

AU - von Ahsen, Oliver

AU - Nastały, Paulina

AU - Röck, Katharina

AU - Boede, Marcel

AU - Peine, Sven

AU - Kuske, Andra

AU - Schmid, Elke

AU - Kneip, Christoph

AU - König, Frank

AU - Rudolph, Marion

AU - Pantel, Klaus

PY - 2016/6/7

Y1 - 2016/6/7

N2 - 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.

AB - 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.

U2 - 10.18632/oncotarget.9004

DO - 10.18632/oncotarget.9004

M3 - SCORING: Journal article

C2 - 27145459

VL - 7

SP - 34930

EP - 34941

JO - ONCOTARGET

JF - ONCOTARGET

SN - 1949-2553

IS - 23

ER -