Challenges in the enumeration and phenotyping of CTC

Frank A W Coumans, Sjoerd T. Ligthart, Jonathan W. Uhr, Leon W M M Terstappen

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Purpose: Presence of circulating tumor cells (CTC) in metastatic carcinoma is associated with poor survival. Phenotyping and genotyping of CTC may permit "real-time" treatment decisions, provided CTCs are available for examination. Here, we investigate what is needed to detect CTC in all patients. Experimental Design: CTCs enumerated in 7.5 mL of blood together with survival from 836 patients with metastatic breast, colorectal, and prostate cancer were used to predict the CTC concentration in the 42% of these patients in whom no CTCs were found and to establish the relation of concentration of CTCs with survival. Influence of different CTC definitions were investigated by automated cell recognition and a flow cytometric assay without an enrichment or permeabilization step. Results: A log-logistic regression of the log of CTC yielded a good fit to the CTC frequency distribution. Extrapolation of the blood volume to 5 L predicted that 99% of patients had at least one CTC before therapy initiation. Survival of patients with EpCAM+, cytokeratin+, CD45- nucleated CTCs is reduced by 6.6 months for each 10-fold CTC increase. Using flow cytometry, the potential three-fold recovery improvement is not sufficient to detect CTC in all patients in 7.5 mL of blood. Conclusions: EpCAM+, cytokeratin+, CD45- nucleated CTCs are present in all patients with metastatic breast, prostate, and colorectal cancer and their frequency is proportional to survival. To serve as a liquid biopsy for the majority of patients, a substantial improvement of CTC yield is needed, which can only be achieved by a dramatic increase in sample volume.

Original languageEnglish (US)
Pages (from-to)5711-5718
Number of pages8
JournalClinical Cancer Research
Volume18
Issue number20
DOIs
StatePublished - Oct 15 2012

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Circulating Neoplastic Cells
Survival
Keratins
Colorectal Neoplasms
Prostatic Neoplasms
Breast Neoplasms
Cell- and Tissue-Based Therapy
Blood Volume
Flow Cytometry
Research Design
Logistic Models

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Coumans, F. A. W., Ligthart, S. T., Uhr, J. W., & Terstappen, L. W. M. M. (2012). Challenges in the enumeration and phenotyping of CTC. Clinical Cancer Research, 18(20), 5711-5718. https://doi.org/10.1158/1078-0432.CCR-12-1585

Challenges in the enumeration and phenotyping of CTC. / Coumans, Frank A W; Ligthart, Sjoerd T.; Uhr, Jonathan W.; Terstappen, Leon W M M.

In: Clinical Cancer Research, Vol. 18, No. 20, 15.10.2012, p. 5711-5718.

Research output: Contribution to journalArticle

Coumans, FAW, Ligthart, ST, Uhr, JW & Terstappen, LWMM 2012, 'Challenges in the enumeration and phenotyping of CTC', Clinical Cancer Research, vol. 18, no. 20, pp. 5711-5718. https://doi.org/10.1158/1078-0432.CCR-12-1585
Coumans FAW, Ligthart ST, Uhr JW, Terstappen LWMM. Challenges in the enumeration and phenotyping of CTC. Clinical Cancer Research. 2012 Oct 15;18(20):5711-5718. https://doi.org/10.1158/1078-0432.CCR-12-1585
Coumans, Frank A W ; Ligthart, Sjoerd T. ; Uhr, Jonathan W. ; Terstappen, Leon W M M. / Challenges in the enumeration and phenotyping of CTC. In: Clinical Cancer Research. 2012 ; Vol. 18, No. 20. pp. 5711-5718.
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