EpCAMhigh and EpCAMlow circulating tumor cells in metastatic prostate and breast cancer patients

Wit, Sanne de; Manicone, Mariangela; Rossi, Elisabetta; Lampignano, Rita; Yang, Liwen; Zill, Beate; Rengel-Puertas, Alvera; Ouhlen, Marianne; Crespo, Mateus; Berghuis, Anne Margreet Sofie; Andree, Kiki; Vidotto, Riccardo; Trapp, Elisabeth; Tzschaschel, M; Colomba, Emeline; Fowler, Gemma; Flohr, Penelope; Rescigno, Pasquale; Fontes, Mariane; Zamarchi, Rita; Fehm, Tanja; Neubauer, Hans; Rack, Brigitte; Alunni-Fabbroni, Marianna; Farace, Françoise; Bono, Johann S. de; IJzerman, Maarten J.; Terstappen, Leonardus Wendelinus Mathias Marie

doi:10.18632/oncotarget.26298

Cited by 79 publications

(82 citation statements)

References 26 publications

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“…This approach was shown to result in a loss of a substantial percentage of EpCAMl ow CTCs, but these cells were shown to have no impact on overall survival (OS) in metastatic breast cancer. Conversely, the presence of EpCAM high cells was demonstrated to be strongly related to poor survival [40]. Examples of EpCAM heterogeneous expression among CTCs from patients with MBC are presented in Figure 2.…”

Section: Changes In Expression; Reversible Re-programingmentioning

confidence: 99%

Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

Fabisiewicz

Szostakowska-Rodzoś

Żaczek

et al. 2020

IJMS

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Breast cancer metastasis is the leading cause of cancer deaths in women and is difficult to combat due to the long periods in which disseminated cells retain a potential to be re-activated and start the relapse. Assessing the number and molecular profile of circulating tumor cells (CTCs) in breast cancer patients, especially in early breast cancer, should help in identifying the possibility of relapse in time for therapeutic intervention to prevent or delay recurrence. While metastatic breast cancer is considered incurable, molecular analysis of CTCs still have a potential to define particular susceptibilities of the cells representing the current tumor burden, which may differ considerably from the cells of the primary tumor, and offer more tailored therapy to the patients. In this review we inspect the routes to metastasis and how they can be linked to specific features of CTCs, how CTC analysis may be used in therapy, and what is the current status of the research and efforts to include CTC analysis in clinical practice.There are two main hypotheses describing cancer dissemination: linear progression, according to which, metastatic potential is gained gradually, and the whole process proceeds in steps and needs time, and parallel progression, according to which dissemination takes place early on, even before clinical manifestation of the tumor [6,7] (Figure 1). In the linear progression model, the evolving primary tumor gives rise to metastases due to increasingly aggressive and invasive phenotypes of the subclones of tumor cells. This model is in agreement with the postulated role of the epithelial-to-mesenchymal transition (EMT) in cancer and assumes active degradation of the stroma and migration into blood vessels by the motile, invasive single cells that broke loose from the epithelial monolayer. In contrast to that, parallel progression postulates intravasation by passive shedding, which may take place shortly after the angiogenic switch, occurring during the early, pre-invasive stage of tumor development [8,9].

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Section: Changes In Expression; Reversible Re-programingmentioning

confidence: 99%

Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

Fabisiewicz

Szostakowska-Rodzoś

Żaczek

et al. 2020

IJMS

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“…Observation in NSCLC, breast and prostate cancer showed that frequently both EpCAM + and EpCAM − CTC populations are present and rarely only one of the two are detected. Moreover, in patients with metastatic NSCLC and prostate cancer we found that the EpCAM + , CK + CTC, and not the EpCAM − , CK + are correlated with poor outcome (46)(47)(48). Hopefully research will be conducted with the newly available technology that can provide in depth information on the frequency of different subpopulations of CTC, other (rare) cell types and their relation with the disease.…”

mentioning

confidence: 99%

CTC Technologies and Tools

Coumans

Dalum

Terstappen³

2018

Cytometry Pt A

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CANCER cells can enter the blood stream. Some of these circulating tumor cells (CTC) extravasate and form distant metastases which ultimately lead to the death of the patient. CTC have been observed quite some time ago (1-3). The major difficulty for the identification of CTC is their extremely low frequency (~1/ml in metastatic patients). When no CTC were detected in a tube of blood of a patient with metastases one always wonders whether they were not present or whether they were missed by the detection technology. Another hurdle is the extensive heterogeneity of the physical and immunological appearance of CTC within and between patients.Tumor cell lines play a pivotal role in both informing technology developers of the probable physical and immunological properties of CTC, as well as in the determination of the analytical accuracy, reproducibility, and linearity of any developed technology. However, tumor cell lines are not CTC. Excellent performance on tumor cell lines does not warrant that (1) the developed technology will actually identify CTC in blood samples of cancer patients nor that (2) these CTC relate to clinical outcome nor that (3) information relevant for treatment can be extracted.At the start of the trajectory toward the FDA cleared CellSearch system very little was known about the CTC frequency and their physical and immunological appearance. CTC enrichment in 10 ml of blood was performed by manual immunomagnetic enrichment targeting EpCAM using the GA73.3 antibody. The enriched cell suspension was fluorescently labeled with the PE-labeled CAM5.2 antibody recognizing cytokeratins 7 and 8, a PerCP-labeled antibody recognizing CD45 and a nucleic acid dye that could be measured in the FITC channel of a flowcytometer. Using this approach, it was first shown that CTC indeed could be detected in 10 ml blood of cancer patients with metastatic disease and at a lesser frequency in patients with no detectable metastasis while few "CTC" were detected in healthy controls (4-8). These results were sufficiently encouraging to further develop the CTC technology and design and conduct clinical studies to explore the clinical utility of CTC. The commercial CellSearch system that was ultimately developed included (1) a blood collection tube to preserve the fragile CTC for a period of up to 96 h, (2) an automated sample preparation system in which (3) the EpCAM antibody was replaced by VU1D9, (4) CAM5.2 cytokeratin antibody was replaced by C11 and A.53B/A2 to increase the range of cytokeratins, (5) the CD45-PerCP was switched to CD45-APC, (6) the nucleic acid dye was switched to DAPI, and (7) the flow cytometer replaced by a semi-automated fluorescence microscope with dedicated software to present CTC candidates to a reviewer. Thanks to an excellent team of reagent developers and engineers the system was reliable and provided accurate results over a large range of spiked tumor cells in blood with a high sensitivity and specificity. Whereas few "CTC" were detected in healthy donors and patients with benign disease...

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“…The fluorescent images were obtained from 7.5 mL blood samples from metastatic prostate and non-small cell lung cancer patients (13)(14)(15). The fluorescent images were obtained from 7.5 mL blood samples from metastatic prostate and non-small cell lung cancer patients (13)(14)(15).…”

Section: Selection Of Fluorescent Cell Images For Ctc Scoringmentioning

confidence: 99%

“…A set of 100 fluorescent cell images comprising of potential CTCs and leukocytes was assembled. The fluorescent images were obtained from 7.5 mL blood samples from metastatic prostate and non-small cell lung cancer patients (13)(14)(15). The blood was processed with the CellSearch system (Menarini Silicon Biosystems, Huntingdon Valley, PA, USA) and the EpCAM depleted blood was collected, passed through microsieves (VyCap, Deventer, The Netherlands), fluorescently labeled and images taken by fluorescent microscopy (13).…”

Section: Selection Of Fluorescent Cell Images For Ctc Scoringmentioning

confidence: 99%

“…The fluorescent images were obtained from 7.5 mL blood samples from metastatic prostate and non-small cell lung cancer patients (13)(14)(15). The blood was processed with the CellSearch system (Menarini Silicon Biosystems, Huntingdon Valley, PA, USA) and the EpCAM depleted blood was collected, passed through microsieves (VyCap, Deventer, The Netherlands), fluorescently labeled and images taken by fluorescent microscopy (13). The images exported from the CellSearch system as well as fluorescent images after filtration of the EpCAM depleted blood were all reanalyzed with the ACCEPT toolbox (https://github.com/LeonieZ/ ACCEPT).…”

Section: Selection Of Fluorescent Cell Images For Ctc Scoringmentioning

confidence: 99%

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How to Agree on a CTC: Evaluating the Consensus in Circulating Tumor Cell Scoring

et al. 2018

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For using counts of circulating tumor cells (CTCs) in the clinic to aid a physician's decision, its reported values will need to be accurate and comparable between institutions. Many technologies have become available to enumerate and characterize CTCs, thereby showing a large range of reported values. Here we introduce an Open Source CTC scoring tool to enable comparison of different reviewers and facilitate the reach of a consensus on assigning objects as CTCs. One hundred images generated from two different platforms were used to assess concordance between 15 reviewers and an expert panel. Large differences were observed between reviewers in assigning objects as CTCs urging the need for computer recognition of CTCs. A demonstration of a deep learning approach on the 100 images showed the promise of this technique for future CTC enumeration. © 2018 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

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EpCAMhigh and EpCAMlow circulating tumor cells in metastatic prostate and breast cancer patients

Cited by 79 publications

References 26 publications

Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

CTC Technologies and Tools

How to Agree on a CTC: Evaluating the Consensus in Circulating Tumor Cell Scoring

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