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Diagnostic and prognostic significance of flow cytometry immunophenotyping in patients with leptomeningeal carcinomatosis

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Abstract

Some patients with epithelial-cell cancers develop leptomeningeal carcinomatosis (LC), a severe complication difficult to diagnose and with an adverse prognosis. This study explores the contribution of flow cytometry immunophenotyping (FCI) to the diagnosis and prognosis of LC. Cerebrospinal fluid (CSF) samples from patients diagnosed with LC were studied using FCI. Expression of the epithelial-cell adhesion molecule (EpCAM) was the criterion used to identify the epithelial cells. To test the diagnostic precision, 144 patients (94 diagnosed with LC) were included. The prognostic value of FCI was evaluated in 72 patients diagnosed with LC and eligible for therapy. Compared with cytology, FCI showed greater sensitivity and negative predictive value (79.79 vs. 50 %; 68.85 vs. 51.55 %, respectively), but lower specificity and positive predictive value (84 vs. 100 %; 90.36 vs. 100 %, respectively). The multivariate analysis revealed that the percentage of CSF EpCAM+ cells predicted an increased risk of death (HR: 1.012, 95 % CI 1.000–1.023; p = 0.041). A cut-off value of 8 % EpCAM+ cells in the CSF distinguished two groups of patients with statistically significant differences in overall survival (OS) (p = 0.018). This cut-off value kept its statistical significance regardless of the absolute CSF cell-count. The FCI study of the CSF improved the sensitivity for diagnosing LC, but refinement of the technique is needed to improve specificity. Furthermore, quantification of CSF EpCAM+ cells was revealed to be an independent prognostic factor for OS in patients with LC eligible for therapy. An 8 % cut-off value contributed to predicting clinical evolution before initiation of therapy.

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Abbreviations

CSF:

Cerebrospinal fluid

EpCAM:

Epithelial-cell adhesion molecule

FCI:

Flow cytometry immunophenotyping

IQR:

Interquartile range

IT:

Intrathecal chemotherapy

KPS:

Karnofsky performance status scale

MRI:

Magnetic resonance imaging

NPV:

Negative predictive value

LC:

Leptomeningeal carcinomatosis

OS:

Overall survival

PPV:

Positive predictive value

RDT:

Radiotherapy

SC:

Systemic chemotherapy

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Acknowledgments

The authors would like to thank all the patients and participants of the Meningeal Carcinomatosis Study Cooperative Group who made this study possible. We also wish to thank Mundipharma Spain for supporting the study, and Lawrence J.C. Baron for editing the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

Local ethics committees of participating centers approved the study, and all patients gave their informed consent prior to their inclusion in the study. All procedures were performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Funding

Mundipharma contributed financial support for sample transportation.

Author information

Authors and Affiliations

  1. Department of Hematology, Flow Cytometry Division, Hospital Universitario de Guadalajara, c/Donantes de sangre s.n., 19002, Guadalajara, Spain

    D. Subirá

  2. Unit of Neuro-Oncology, Departments of Oncology and Neurology, Hospital Universitario de Bellvitge-ICO Duran i Reynals, Avda. Gran Vía s/n km 2.7, Hospitalet de Llobregat, 08907, Barcelona, Spain

    M. Simó & J. Bruna

  3. Unilabs Diagnósticos, SLU, c/Juan Esplandiú 15, 28007, Madrid, Spain

    J. Illán

  4. Department of Hematology, Fundación Jiménez Díaz, Plaza Cristo Rey 1, 28040, Madrid, Spain

    C. Serrano, S. Castañón & R. Gonzalo

  5. Clinical Epidemiology Unit, Hospital Infanta Cristina, Avda. 9 de Junio, 2, Parla, 28981, Madrid, Spain

    J. J. Granizo

  6. Department of Oncology, Hospital del Mar, Paseo Marítimo 25-29, 8003, Barcelona, Spain

    M. Martínez-García

  7. Department of Oncology, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Paseo de San Vicente, 58-182, Salamanca, 37007, Spain

    M. Navarro

  8. Department of Neurology, Hospital Infanta Elena/Hospital General de Villalba/Hospital Universitario Rey Juan Carlos, c/Gladiolo s/n., 28933, Móstoles, Spain

    J. Pardo

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  1. D. Subirá
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  2. M. Simó
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  6. R. Gonzalo
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  8. M. Martínez-García
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  10. J. Pardo
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  11. J. Bruna
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Correspondence to D. Subirá.

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Subirá, D., Simó, M., Illán, J. et al. Diagnostic and prognostic significance of flow cytometry immunophenotyping in patients with leptomeningeal carcinomatosis. Clin Exp Metastasis 32, 383–391 (2015). https://doi.org/10.1007/s10585-015-9716-3

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