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Open Access Technical advance

Development of a new method for identification and quantification in cerebrospinal fluid of malignant cells from breast carcinoma leptomeningeal metastasis

Emilie Le Rhun1*, Frédéric Massin2, Qian Tu3, Jacques Bonneterre4, Marcelo De Carvalho Bittencourt5 and Gilbert C Faure6

Author affiliations

1 Neurology, Breast Unit, Deparment of Medical Oncology, Oscar Lambret Center, Lille, France and Neuro-oncology, University Hospital, Lille, France

2 CHU Nancy, Nancytomique, Laboratoire d’Immunologie, Pôle Laboratoires, Vandoeuvre lès Nancy, Nancy, France

3 CHU Nancy, Nancytomique, Laboratoire d’Immunologie, Pôle Laboratoires, Vandoeuvre lès Nancy, Nancy, France

4 Breast Unit, Department of Medical Oncology, Centre Oscar Lambret, Lille, France and University of Lille Nord de France, Lille, France

5 CHU Nancy, Nancytomique, Laboratoire d’Immunologie, Pôle Laboratoires, Vandoeuvre lès Nancy, France and Université Henri Poincaré, Faculté de Médecine, Vandoeuvre lès Nancy, EA4369 RHEM, Nancy, France

6 CHU Nancy, Nancytomique, Laboratoire d’Immunologie, Pôle Laboratoires, Vandoeuvre lès Nancy, France and Université Henri Poincaré, Faculté de Médecine, Vandoeuvre lès Nancy, EA4369 RHEM, Nancy, France

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Citation and License

BMC Clinical Pathology 2012, 12:21  doi:10.1186/1472-6890-12-21

Published: 12 November 2012

Abstract

Background

The diagnosis of leptomeningeal metastasis (LM) in patients with solid tumors remains difficult. The usual diagnostic methods of cytomorphological assessment of cerebro-spinal fluid (CSF) and gadolinium enhanced MRI of the entire neuraxis lack both specificity and sensitivity. The Veridex CellSearch® technology has been designed for the detection of circulating tumor cells (CTC) in blood from cancer patients and validated for the follow-up and prognosis of breast, prostate, colorectal, and lung cancer. Our aim was to adapt this technology for the detection and the enumeration of tumor cells in the CSF of breast cancer patients presenting with LM.

Methods

On the occasion of a randomized phase III study evaluating the role of the intrathecal treatment in LM from breast cancer (DEPOSEIN, EudraCT N°: 2010-023134-23), the CellSearch® technology was adapted to direct enrichment, enumeration and visualization of tumor cells in 5 mL CSF samples, collected on CellSave® Preservative Tubes and analyzed within 3 days after CSF sampling.

Results

Sixteen CSF of 8 patients with primary breast cancer presenting with LM were studied. EpCAM+/cytokeratin + cells with typical morphology could be observed and enumerated sequentially with reproducible results in low or elevated numbers in 8 patients.

Conclusion

This methodology, established on a limited volume of sample and allowing delayed processing, could prove of great interest in the diagnosis and follow-up of cancer patients with LM, especially to appreciate the efficacy of chemotherapy.

Keywords:
Leptomeningeal metastasis; Neoplastic meningitis; Meningeal carcinomatosis; CellSearch® technology; Immunomagnetic enrichment; CSF cytology