title: Detection of cerebrospinal fluid tumor cells and its clinical relevance in leptomeningeal metastasis of breast cancer.
abstract: Circulating tumor cells are commonly observed in the peripheral blood of advanced breast cancer patients. We tested the feasibility of tumor cell detection in the cerebrospinal fluid (CSF) and studied its clinical relevance in leptomeningeal metastasis (LM) of breast cancer. CSF samples were collected from 38 metastatic breast cancer patients known or suspected to have LM. Control CSF samples were collected from 14 individuals without solid tumor malignancy. We used a modified CellSearch™ assay and an alternative EPCAM-based method involving immunomagnetic enrichment followed by flow cytometry (IE/FC) to enumerate CSF tumor cells (CSFTCs). CSFTCs were assayed at time of LM diagnosis and over the course of LM-directed therapy. We analyzed a total of 102 CSF samples with modified CellSearch™. The CSFTC counts were strongly correlated with the corresponding IE/FC results (Pearson's r = 0.94). Twenty-eight out of 30 samples in which malignant cells were identified by CSF cytology were CSFTC-positive by modified CellSearch™. Baseline CSFTC levels from 21 patients eventually diagnosed with LM were significantly higher than the controls (p = 0.0202), whereas 13 patients deemed not to have LM showed CSFTC results indistinguishable from the controls. In patients with serial samples, it was possible to monitor CSFTC levels as a potential biomarker of treatment response. CSFTC detection using a modified CellSearch™ assay demonstrated high sensitivity in detecting malignant cells in CSF and may be a promising method for diagnosing LM and monitoring LM during treatment.
authors.affiliation: Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 2340 Sutter Street, San Francisco, CA, 94115, USA.
authors.forename: Jin Sun
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 2340 Sutter Street, San Francisco, CA, 94115, USA.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Melisko
authors.affiliation: Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 2340 Sutter Street, San Francisco, CA, 94115, USA.
authors.forename: Mark Jesus M
authors.initials: MJ
authors.lastname: Magbanua
authors.affiliation: Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 2340 Sutter Street, San Francisco, CA, 94115, USA.
authors.forename: Andrea T
authors.initials: AT
authors.lastname: Kablanian
authors.affiliation: Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 2340 Sutter Street, San Francisco, CA, 94115, USA.
authors.forename: Janet H
authors.initials: JH
authors.lastname: Scott
authors.affiliation: Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 2340 Sutter Street, San Francisco, CA, 94115, USA.
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.affiliation: Division of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 2340 Sutter Street, San Francisco, CA, 94115, USA. john.park@ucsf.edu.
authors.forename: John W
authors.initials: JW
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000134:cerebrospinal fluid* / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002452:Cell Count; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018189:Immunomagnetic Separation; D008577:Meningeal Neoplasms / Q000175:diagnosis* / Q000556:secondary*; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism / Q000473:pathology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule
keywords: Cerebrospinal fluid tumor cells; Circulating tumor cells; Leptomeningeal metastasis; Metastatic breast cancer