Quantitative RT‐PCR analysis of PSA and prostate‐specific membrane antigen mRNA to detect circulating tumor cells improves recurrence‐free survival nomogram prediction after radical prostatectomy

Yates, David R.; Rouprêt, Morgan; Drouin, S.; Compérat, Éva; Ricci, Sylvie; Lacave, Roger; Sèbe, Philippe; Cancel‐Tassin, Géraldine; Bitker, Marc‐Olivier; Cussenot, Olivier

doi:10.1002/pros.22488

Cited by 34 publications

(32 citation statements)

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“…Besides, qRT-PCR targeting the PSMA transcript was applied to identify CTCs in patients before and after radical prostatectomy [15]. However, to our best knowledge, this is the first study implementing PSMA staining in the FDA-cleared CellSearch ® system that offers the possibility to capture CTCs in a standardized and highly reproducible manner within the clinical context.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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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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Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…To date, the mRNA encoding PSA has been the most extensively studied in clinical trials (63,69,72). Mohamadi et al (73) developed a velocity valley chip to efficiently capture magnetic nanoparticle-bound CTCs.…”

Section: Enrichment and Detection Strategies For Ctcmentioning

confidence: 99%

“…The approach was successfully validated using samples collected from patients with PCa: CTCs and PSA mRNA sequences were detected in all cancer patient samples and not in the healthy controls. In addition, quantitative RT-PCR analysis of PSA and PSMA mRNA to detect circulating tumor cells improves recurrence-free survival nomogram prediction following radical prostatectomy (72). Furthermore, androgen receptor (AR), kallikrein-related peptidase (KLK)2, KLK3, PCa antigen 3 (PCA3), transmembrane protease serine 2 and ETS-related fusion gene (TMPRSS2-ERG), AR splice variant 7 messenger RNA (AR-V7) and prostate stem cell antigen mRNA are also utilized to identify PCTCs (63,69,74–76).…”

Section: Enrichment and Detection Strategies For Ctcmentioning

confidence: 99%

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Circulating tumor cells in prostate cancer: Precision diagnosis and therapy

et al. 2017

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The primary cause of tumor-associated mortality in prostate cancer (PCa) remains distant metastasis. The dissemination of tumor cells from the primary tumor to distant sites through the bloodstream cannot be detected early by standard imaging methods. Circulating tumor cells (CTCs) represent an effective prognostic and predictive biomarker, which are able to monitor efficacy of adjuvant therapies, detect early development of metastases, and finally, assess therapeutic responses of advanced disease earlier than traditional diagnostic methods. In addition, since repeated tissue biopsies are invasive, costly and not always feasible, the assessment of tumor characteristics on CTCs, by a peripheral blood sample as a liquid biopsy, represents an attractive opportunity. The implementation of molecular and genomic characterization of CTCs may contribute to improve the treatment selection and thus, to move toward more precise diagnosis and therapy in PCa. The present study summarizes the current advances in CTC enrichment and detection strategies and reviews how CTCs may contribute to significant insights in the metastatic process, as well as how they may be utilized in clinical application in PCa. Although it is proposed that CTCs may offer insights into the prognosis and management of PCa, there are a number of challenges in the study of circulating tumor cells, and their clinical utility remains under investigation.

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“…In one study, PSA mRNA copy number used as a surrogate for CTC count was predictive of recurrence after radical prostatectomy (Yates et al, 2012). Several studies have shown significant differences in PSA and PSMA mRNA copy number among patients with benign prostatic hypertrophy, localized prostate cancer, and metastatic disease (Zhang et al, 2008; Kalfazade et al, 2009).…”

Section: Ctc Detection Methodsmentioning

confidence: 99%

Isolation and characterization of circulating tumor cells in prostate cancer

Diamond¹,

Lee²,

Akhtar³

et al. 2012

Front. Oncol.

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Circulating tumor cells (CTCs) are tumor cells found in the peripheral blood that putatively originate from established sites of malignancy and likely have metastatic potential. Analysis of CTCs has demonstrated promise as a prognostic marker as well as a source of identifying potential targets for novel therapeutics. Isolation and characterization of these cells for study, however, remain challenging owing to their rarity in comparison with other cellular components of the peripheral blood. Several techniques that exploit the unique biochemical properties of CTCs have been developed to facilitate their isolation. Positive selection of CTCs has been achieved using microfluidic surfaces coated with antibodies against epithelial cell markers or tumor-specific antigens such as EpCAM or prostate-specific membrane antigen (PSMA). Following isolation, characterization of CTCs may help guide clinical decision making. For instance, molecular and genetic characterization may shed light on the development of chemotherapy resistance and mechanisms of metastasis without the need for a tissue biopsy. This paper will review novel isolation techniques to capture CTCs from patients with advanced prostate cancer, as well as efforts to characterize the CTCs. We will also review how these analyzes can assist in clinical decision making. Conclusion: The study of CTCs provides insight into the molecular biology of tumors of prostate origin that will eventually guide the development of tailored therapeutics. These advances are predicated on high yield and accurate isolation techniques that exploit the unique biochemical features of these cells.

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Quantitative RT‐PCR analysis of PSA and prostate‐specific membrane antigen mRNA to detect circulating tumor cells improves recurrence‐free survival nomogram prediction after radical prostatectomy

Abstract: Data from modern quantitative RT-PCR to detect circulating prostate-derived PSA and PSM mRNA pre- and post-RP improves the accuracy of the Kattan nomogram to predict biochemical recurrence.

Cited by 34 publications

References 46 publications

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

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

Circulating tumor cells in prostate cancer: Precision diagnosis and therapy

Isolation and characterization of circulating tumor cells in prostate cancer

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