Research Papers:

Identification and enumeration of circulating tumor cells in the cerebrospinal fluid of breast cancer patients with central nervous system metastases

Akshal S. Patel, Joshua E. Allen, David T. Dicker, Kristi L. Peters, Jonas M. Sheehan, Michael J. Glantz and Wafik S. El-Deiry _

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Oncotarget. 2011; 2:752-760. https://doi.org/10.18632/oncotarget.336

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Akshal S. Patel1,2,*, Joshua E. Allen1,3,*, David T. Dicker1, Kristi L. Peters1, Jonas M. Sheehan2, Michael J. Glantz2 and Wafik S. El-Deiry1,3

1Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Department of Medicine (Hematology/Oncology), Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA, USA

2Department of Neurological Surgery, Penn State Hershey Medical Center, Hershey, PA, USA

3Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

*Denotes equal contribution

Received: October 7, 2011; Accepted: October 7, 2011; Published: October 8, 2011;

Keywords: circulating tumor cells, carcinomatous meningitis, breast cancer, brain metastases, intrathecal chemotherapy, cancer monitoring


Wafik S. El-Deiry, email:


The number of circulating tumor cells (CTCs) in the peripheral blood of metastatic breast cancer patients is now an established prognostic marker. While the central nervous system is a common site of metastasis in breast cancer, the standard marker for disease progression in this setting is cerebrospinal fluid (CSF) cytology. However, the significance of CSF cytology is unclear, requires large sample size, is insensitive and subjective, and sometimes yields equivocal results. Here, we report the detection of breast cancer cells in CSF using molecular markers by adapting the CellSearch system (Veridex). We used this platform to isolate and enumerate breast cancer cells in CSF of breast cancer patients with central nervous system (CNS) metastases. The number of CSF tumor cells correlated with tumor response to chemotherapy and were dynamically associated with disease burden. This CSF tumor cell detection method provides a semi-automated molecular analysis that vastly improves the sensitivity, reliability, objectivity, and accuracy of detecting CSF tumor cells compared to CSF cytology. CSF tumor cells may serve as a marker of disease progression and early-stage brain metastasis in breast cancer and potentiate further molecular analysis to elucidate the biology and significance of tumor cells in the CSF.

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