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limitations of CTCs detection

Tuesday 17 March 2015

Despite the numerous scientific publications related to CTC detection in cancer patients, the physician does not use this biomarker in routine clinical practice. This can be explained by the large number of methods available for CTC detection and by the difficulty of the physician and the biologist to select the optimal method for use.

Lung cancer

It is noteworthy that the only FDA approved method for CTC detection, the CellSearch method (Janssen Diagnostics Company, USA), has been approved for CTC detection in metastatic breast, prostate and colon cancer patients, but not in metastatic lung cancer patients. This has added some confusion to the use of this indirect technology for lung cancer patient CTC detection.

Moreover, since CTCs that have undergone epithelial-mesenchymal transition cannot express epithelial biomarkers, the CellSearch system can certainly miss the detection of a subpopulation of CTCs of interest in lung cancer patients.

Direct technologies for CTC detection in lung cancer, such as the ISET approach (developed by Rarecells Company, France), are certainly strongly attractive, but the results obtained by different teams probably need to be validated in independent and large multicenter studies.

ISET allows cytological characterization of the CTCs isolated from lung cancer patients, according to the classical morphological criteria used by the cytopathologists for distinguishing between benign and malignant epithelial cells.

Moreover this approach allows an immunocytochemical assessment of CTCs expressing epithelial and/or mesenchymal biomarkers.

Other direct technology, such as those developed by ScreenCell company in France, allows morphological assessment of CTCs in lung cancer patients too.

Many other methods are currently being developed for CTC characterization, such as a method allowing functional evaluation the CTCs and characterization of a subpopulation of malignant cells.


- Huang T, Jia CP, Jun Y, et al. Highly sensitive enumeration of circulating tumor cells in lung cancer patients using a size-based filtration microfluidic chip. Biosens Bioelectron 2014;51:213-8. []

- Hofman VJ, Ilie MI, Bonnetaud C, et al. Cytopathologic detection of circulating tumor cells using the isolation by size of epithelial tumor cell method: promises and pitfalls. Am J Clin Pathol 2011;135:146-56. []

- Hofman V, Long E, Ilie M, et al. Morphological analysis of circulating tumour cells in patients undergoing surgery for non-small cell lung carcinoma using the isolation by size of epithelial tumour cell (ISET) method. Cytopathology 2012;23:30-8. []

- Yao X, Choudhury AD, Yamanaka YJ, et al. Functional analysis of single cells identifies a rare subset of circulating tumor cells with malignant traits. Integr Biol (Camb) 2014;6:388-98. []