Characterization of different CTC subpopulations in non-small cell lung cancer.
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.
Department of Tumour Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Annkathrin
A
Hanssen
QIAGEN Hannover GmbH, Germany.
Jenny
J
Wagner
Department of Tumour Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Tobias M
TM
Gorges
Department of Tumour Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.|Center for Neurology, Neurosurgery, and Psychiatry, Department of Psychiatry, Campus Benjamin Franklin, Charité University Hospital Berlin, Germany.
Aline
A
Taenzer
Department of General, Visceral and Thoracic Surgery, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Faik G
FG
Uzunoglu
Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
Christiane
C
Driemel
Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
Nikolas H
NH
Stoecklein
Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
Wolfram T
WT
Knoefel
Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
Sebastian
S
Angenendt
QIAGEN Hannover GmbH, Germany.
Siegfried
S
Hauch
Department of Internal Medicine II and Clinic (Oncology Centre), University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Djordje
D
Atanackovic
Department of Tumour Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.|Department of Internal Medicine II and Clinic (Oncology Centre), University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Sonja
S
Loges
Department of Tumour Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Sabine
S
Riethdorf
Department of Tumour Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Klaus
K
Pantel
Department of Tumour Biology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Harriet
H
Wikman
D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000071858:Epithelial Cell Adhesion Molecule / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism; D046888:Tissue Array Analysis; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; C512478:EGFR protein, human; C581292:ERBB3 protein, human; D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D020893:Receptor, ErbB-3