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Ann Oncol. 2017 Jul 1;28(7):1523-1531. doi: 10.1093/annonc/mdx156.

A prospective examination of circulating tumor cell profiles in non-small-cell lung cancer molecular subgroups.

Author information

INSERM U981, University of Paris-Sud XI, Translational Research Laboratory, Gustave Roussy Cancer Campus, Villejuif, France.
Department of Biostatistics and Epidemiology, Gustave Roussy Cancer Campus, Villejuif, France.
Department of Cancer Medicine, Gustave Roussy Cancer Campus, Villejuif, France.
Drug Development Department, Gustave Roussy Cancer Campus, Villejuif, France.
Department of Radiology, Gustave Roussy Cancer Campus, Villejuif, France.



We report the first study examining the clinical, numerical and biological properties of circulating tumor cells according to molecular subtypes of non-small-cell lung cancer.

Patients and methods:

125 patients with treatment-naïve stage IIIb-IV NSCLC were prospectively recruited for CellSearch analysis. Anti-vimentin antibody was included for examination of CTCs to assess their mesenchymal character. Associations of total CTCs and vimentin-positive (vim +) CTCs with clinical characteristics, tumor genotype, and survival were assessed.


51/125 patients (40.8%) were total CTC+ and 26/125 (20.8%) were vim CTC+ at baseline. Multivariate analysis showed patients with ≥5 total CTCs had significantly reduced OS (HR 0.55, 95% CI 0.33-0.92, P = 0.022) but not PFS (HR 0.68, 95% CI 0.42-1.1, P = 0.118) compared to patients with <5 total CTCs. No OS difference was evident between vim+ CTC and vim-negative CTC patients overall (HR 1.24, 95% CI 0.67-2.28, P = 0.494), but after subdivision according to NSCLC driver mutation, we found an increase of vim+ CTCs in the EGFR-mutated subgroup (N = 21/94 patients; mean 1.24 vs 1.22 vim+ CTCs, P = 0.013), a reduction of total CTCs in the ALK-rearranged subgroup (N = 13/90 patients; mean 1.69 vs 5.82 total CTCs, P = 0.029), and a total absence of vim+ CTCs in KRAS-mutated adenocarcinomas (N = 19/78 patients; mean 0 vs 1.4 vim+ CTCs, P = 0.006).


We validate that the baseline presence of ≥5 total CTCs in advanced NSCLC confers a poor prognosis. CTCs from EGFR-mutant NSCLC express epithelial-mesenchymal transition characteristics, not seen in CTCs from patients with KRAS-mutant adenocarcinoma.


CTC; EMT; biomarker; circulating tumor cell; non-small-cell lung cancer; vimentin

[Indexed for MEDLINE]

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