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Towards an optimized platform for the detection, enrichment, and semi-quantitation circulating tumor cells

  • Preclinical Study
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Abstract

Metastasis describes the process of migration of a frequently clinically occult circulating tumor cell (CTC) from the primary lesion to a new location and the subsequent formation of an overt growth. We and others have shown that the detection and quantitation of these cells has significant prognostic value, however there still remains no consensus as to the optimal methods to achieve this. The work described herein therefore considered various techniques, from storage and sample processing to data acquisition and analysis, to find an optimal combination of methods for an effective and practical platform for the detection of CTCs in peripheral blood. A dual-antigen epithelial cell enrichment procedure followed by a multi-marker QPCR analysis demonstrated the highest sensitivity and specificity, with the ability to detect as few as 10 tumor cells from a background of 106 peripheral blood mononuclear cells. Using these techniques in conjunction with a quadratic linear discriminant analysis (QDA) resulted in a platform able to generate this data and then combine it a single score for each patient, in which positivity reflected tumor cell presence, and negativity represented tumor cell absence. This assay was able to correctly determine tumor cell presence or absence in 100% of healthy controls and 84% of metastatic patients in a validation cohort of 39 individuals. This platform represents a highly sensitive and specific assay which could augment current routine assays for CTCs in the clinic.

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Acknowledgements

The authors would like to acknowledge Helgi Helgason and Sjoerd Rodenhuis for providing clinical data and samples. This work was supported by the Sixth Framework Program of the European Commission as part of the international DISMAL collaboration for research into disseminated epithelial malignancies.

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Authors and Affiliations

  1. Division of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands

    T. J. Molloy, A. J. Bosma & Laura J. van’t Veer

  2. Department of Pathology, The Netherlands Cancer Institute, 121 Plesmanlaan, Amsterdam, 1066 CX, The Netherlands

    Laura J. van’t Veer

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  1. T. J. Molloy
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  2. A. J. Bosma
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  3. Laura J. van’t Veer
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Correspondence to Laura J. van’t Veer.

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Molloy, T.J., Bosma, A.J. & van’t Veer, L.J. Towards an optimized platform for the detection, enrichment, and semi-quantitation circulating tumor cells. Breast Cancer Res Treat 112, 297–307 (2008). https://doi.org/10.1007/s10549-007-9872-5

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  • DOI: https://doi.org/10.1007/s10549-007-9872-5

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