Research Papers:

Establishment of a multimarker qPCR panel for the molecular characterization of circulating tumor cells in blood samples of metastatic breast cancer patients during the course of palliative treatment

Maren Bredemeier _, Philippos Edimiris, Mitra Tewes, Pawel Mach, Bahriye Aktas, Doreen Schellbach, Jenny Wagner, Rainer Kimmig and Sabine Kasimir-Bauer

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Oncotarget. 2016; 7:41677-41690. https://doi.org/10.18632/oncotarget.9528

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Maren Bredemeier1, Philippos Edimiris1, Mitra Tewes2, Pawel Mach1, Bahriye Aktas1, Doreen Schellbach3, Jenny Wagner3, Rainer Kimmig1, Sabine Kasimir-Bauer1

1Department of Gynecology and Obstetrics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

2Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany

3QIAGEN Hannover GmbH, Langenhagen, Germany

Correspondence to:

Maren Bredemeier, email: maren.bredemeier@uk-essen.de

Keywords: circulating tumor cells, multimarker gene panel, metastatic breast cancer

Received: October 21, 2015     Accepted: April 16, 2016     Published: May 20, 2016


Background: Circulating tumor cells (CTC) are discussed to be an ideal surrogate marker for individualized treatment in metastatic breast cancer (MBC) since metastatic tissue is often difficult to obtain for repeated analysis. We established a nine gene qPCR panel to characterize the heterogeneous CTC population in MBC patients including epithelial CTC, their receptors (EPCAM, ERBB2, ERBB3, EGFR) CTC in Epithelial-Mesenchymal-Transition [(EMT); PIK3CA, AKT2), stem cell-like CTC (ALDH1) as well as resistant CTC (ERCC1, AURKA] to identify individual therapeutic targets.

Results: At TP0, at least one marker was detected in 84%, at TP1 in 74% and at TP2 in 79% of the patients, respectively. The expression of ERBB2, ERBB3 and ERCC1 alone or in combination with AURKA was significantly associated with therapy failure. ERBB2 + CTC were only detected in patients not receiving ERBB2 targeted therapies which correlated with no response. Furthermore, patients responding at TP2 had a significantly prolonged overall-survival than patients never responding (p = 0.0090).

Patients and Methods: 2 × 5 ml blood of 62 MBC patients was collected at the time of disease progression (TP0) and at two clinical staging time points (TP1 and TP2) after 8–12 weeks of chemo-, hormone or antibody therapy for the detection of CTC (AdnaTest EMT-2/StemCell Select™, QIAGEN Hannover GmbH, Germany). After pre-amplification, multiplex qPCR was performed. Establishment was performed using various cancer cell lines. PTPRC (Protein tyrosine phosphatase receptor type C) and GAPDH served as controls.

Conclusions: Monitoring MBC patients using a multimarker qPCR panel for the characterization of CTC might help to treat patients accordingly in the future.

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