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Sci Rep. 2016 Jun 15;6:28010. doi: 10.1038/srep28010.

Characterization of different CTC subpopulations in non-small cell lung cancer.

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Department of Tumour Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
QIAGEN Hannover GmbH, Germany.
Center for Neurology, Neurosurgery, and Psychiatry, Department of Psychiatry, Campus Benjamin Franklin, Charité University Hospital Berlin, Germany.
Department of General, Visceral and Thoracic Surgery, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
Department of Internal Medicine II and Clinic (Oncology Centre), University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.


Circulating tumour cells (CTCs) serve as valuable biomarkers. However, EpCAM positive CTCs are less frequently detected in NSCLC patients compared to other epithelial tumours. First, EpCAM protein expression was analysed in primary and metastatic lung cancer tissue. In both groups 21% of the samples were EpCAM negative. Second, the CellSearch system identified 15% of patients (n = 48) as CTC positive whereas a multiplex RT-PCR for PIK3CA, AKT2, TWIST, and ALDH1 following EGFR, HER2 and EpCAM based enrichment detected CTCs in 29% of the patients. Interestingly, 86% of CTC positive patients were found to express ALDH1. Only 11% of the patients were CTC-positive by both techniques. CTC positivity was associated with patient disease state when assessed by the multiplex RT-PCR assay (p = 0.015). Patients harbouring tumours with an altered EGFR genotype were more frequently CTC-positive compared to patients with EGFR wildtype tumours. In subsets of patients, CTCs were found to express genes involved in resistance to therapy such as HER3 and MET. In conclusion, using multiple targets for CTC capture and identification increases the sensitivity of CTC detection in NSCLC patients, which can be explained by the presence of different CTC subtypes with distinct molecular features.

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