EpCAM-based flow cytometry in cerebrospinal fluid greatly improves diagnostic accuracy of leptomeningeal metastases from epithelial tumors

Kerklaan, Bojana Milojkovic; Pluim, Dick; Bol, Mijke; Hofland, Ingrid; Westerga, Johan; Tinteren, Harm van; Beijnen, Jos H.; Boogerd, Willem; Schellens, Jan H.M.; Brandsma, Dieta

doi:10.1093/neuonc/nov273

Cited by 64 publications

(52 citation statements)

References 24 publications

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Section: Flow Cytometrymentioning

confidence: 86%

“…102 Although this study was limited by a small number of participants (n = 29), its results suggest that flow cytometry warrants further study for diagnosing neoplastic meningitis. 102 However, a caveat to the use of flow cytometry on CSF samples is its low cell number and suboptimal cell environment, meaning that cancer cells degenerate following their in situ removal and even more so when repeatedly centrifuged. Other potentially significant limitations of flow cytometry include a high rate of false-positive results at low cell counts (< 25 cells/μL) and an inability to provide differential data (poor differentiation between monocytes and eosinophils and an inability to detect mitoses and neoplastic cells).…”

Section: Flow Cytometrymentioning

confidence: 86%

See 1 more Smart Citation

Clinical Presentation, Diagnosis, and Radiological Findings of Neoplastic Meningitis

Rigakos¹,

Liakou²,

Felipe

et al. 2017

Cancer Control

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Section: Flow Cytometrymentioning

confidence: 86%

Section: Flow Cytometrymentioning

confidence: 86%

Clinical Presentation, Diagnosis, and Radiological Findings of Neoplastic Meningitis

Rigakos¹,

Liakou²,

Felipe

et al. 2017

Cancer Control

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“…FC is a sensitive technique for the detection of abnormal lymphoid populations in CSF [26,27]. Flow cytometric analysis shows a high sensitivity and specificity for the diagnosis of carcinomatous meningitis [28,29]. The utility of FC lies in the ability to immunophenotype rare cells.…”

Section: Flow Cytometric Evaluation Of Csf Samplesmentioning

confidence: 99%

Flow Cytometry of Nonhematopoietic Neoplasms

Pillai

Dorfman

2016

Acta Cytologica

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Many epithelial neoplasms can be analyzed by flow cytometry (FC), particularly from serous cavity effusion samples, using EpCAM, a cell adhesion molecule expressed on most normal epithelial cells and expressed at a higher level in most epithelial neoplasms. A simple 3-color flow cytometric panel can provide a high sensitivity and specificity compared to cytomorphology. FC provides more rapid immunophenotyping than conventional immunohistochemical staining, can identify rare malignant cells that could be missed by a cytological exam alone, and can be utilized to evaluate limited samples such as cerebrospinal fluid or fine-needle aspiration samples. Flow cytometric analysis for epithelial antigens can be combined with DNA ploidy analysis or assessment of the nucleus-to-cytoplasm ratio. Panels of flow cytometric markers are useful for the assessment of pediatric nonhematopoietic neoplasms, including neuroblastomas, primitive neuroectodermal tumors, Wilms' tumor, rhabdomyosarcomas, germ cell tumors, and hemangiopericytomas, as well as small-round-blue-cell tumors in adults, including small-cell carcinomas.

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“…However, studies regarding the role of CSF flow cytometry in solid tumors LM are still limited [24–27]. …”

Section: Introductionmentioning

confidence: 99%

Overexpression of syndecan-1, MUC-1, and putative stem cell markers in breast cancer leptomeningeal metastasis: a cerebrospinal fluid flow cytometry study

Cordone¹,

Masi²,

Summa³

et al. 2017

Breast Cancer Res

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BackgroundCancer is a mosaic of tumor cell subpopulations, where only a minority is responsible for disease recurrence and cancer invasiveness. We focused on one of the most aggressive circulating tumor cells (CTCs) which, from the primitive tumor, spreads to the central nervous system (CNS), evaluating the expression of prognostic and putative cancer stem cell markers in breast cancer (BC) leptomeningeal metastasis (LM).MethodsFlow cytometry immunophenotypic analysis of cerebrospinal fluid (CSF) samples (4.5 ml) was performed in 13 consecutive cases of BCLM. Syndecan-1 (CD138), MUC-1 (CD227) CD45, CD34, and the putative cancer stem cell markers CD15, CD24, CD44, and CD133 surface expression were evaluated on CSF floating tumor cells. The tumor-associated leukocyte population was also characterized.ResultsDespite a low absolute cell number (8 cell/μl, range 1–86), the flow cytometry characterization was successfully conducted in all the samples. Syndecan-1 and MUC-1 overexpression was documented on BC cells in all the samples analyzed; CD44, CD24, CD15, and CD133 in 77%, 75%, 70%, and 45% of cases, respectively. A strong syndecan-1 and MUC-1 expression was also documented by immunohistochemistry on primary breast cancer tissues, performed in four patients. The CSF tumor population was flanked by T lymphocytes, with a different immunophenotype between the CSF and peripheral blood samples (P ≤ 0.02).ConclusionsFlow cytometry can be successfully employed for solid tumor LM characterization even in CSF samples with low cell count. This in vivo study documents that CSF floating BC cells overexpress prognostic and putative cancer stem cell biomarkers related to tumor invasiveness, potentially representing a molecular target for circulating tumor cell detection and LM treatment monitoring, as well as a primary target for innovative treatment strategies. The T lymphocyte infiltration, documented in all CSF samples, suggests a possible involvement of the CNS lymphatic system in both lymphoid and cancer cell migration into and out of the meninges, supporting the extension of a new form of cellular immunotherapy to LM. Due to the small number of cases, validation on large cohorts of patients are warranted to confirm these findings and to evaluate the impact and value of these results for diagnosis and management of LM.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-017-0827-4) contains supplementary material, which is available to authorized users.

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EpCAM-based flow cytometry in cerebrospinal fluid greatly improves diagnostic accuracy of leptomeningeal metastases from epithelial tumors

Abstract: NCT01713699.

Cited by 64 publications

References 24 publications

Clinical Presentation, Diagnosis, and Radiological Findings of Neoplastic Meningitis

Clinical Presentation, Diagnosis, and Radiological Findings of Neoplastic Meningitis

Flow Cytometry of Nonhematopoietic Neoplasms

Overexpression of syndecan-1, MUC-1, and putative stem cell markers in breast cancer leptomeningeal metastasis: a cerebrospinal fluid flow cytometry study

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