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YKL-40 and MMP-9 as serum markers for patients with primary central nervous system lymphoma

Authors

  • Andreas F. Hottinger MD, PhD,

    1. Brain Tumor Center andMemorial Sloan-Kettering Cancer Center, New York, NY
    2. Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
    3. Department of Oncology, Geneva University Hospital, Geneva, Switzerland
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  • Fabio M. Iwamoto MD,

    1. Brain Tumor Center andMemorial Sloan-Kettering Cancer Center, New York, NY
    2. Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
    3. Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD
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  • Sasan Karimi MD,

    1. Brain Tumor Center andMemorial Sloan-Kettering Cancer Center, New York, NY
    2. Departmetnt of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY
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  • Elyn Riedel MA,

    1. Epidemiology-Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY
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  • Jocelynn Dantis CCRP,

    1. Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
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  • Joseph Park BS,

    1. Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
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  • Katherine S. Panageas DrPH,

    1. Epidemiology-Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY
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  • Andrew B. Lassman MD,

    1. Brain Tumor Center andMemorial Sloan-Kettering Cancer Center, New York, NY
    2. Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
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  • Lauren E. Abrey MD,

    1. Brain Tumor Center andMemorial Sloan-Kettering Cancer Center, New York, NY
    2. Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
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  • Martin Fleisher PhD,

    1. Clinical Laboratories, Memorial Sloan-Kettering Cancer Center, New York, NY
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  • Eric C. Holland MD, PhD,

    1. Brain Tumor Center andMemorial Sloan-Kettering Cancer Center, New York, NY
    2. Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
    3. Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, NY
    4. Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY
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  • Lisa M. DeAngelis MD,

    1. Brain Tumor Center andMemorial Sloan-Kettering Cancer Center, New York, NY
    2. Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
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  • Adília Hormigo MD, PhD

    Corresponding author
    1. Brain Tumor Center andMemorial Sloan-Kettering Cancer Center, New York, NY
    2. Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY
    • Department of Neurology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021
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Abstract

Objective:

To evaluate YKL-40 and MMP-9 proteins as tumor biomarkers in serum samples from patients with primary central nervous system lymphoma (PCNSL).

Methods:

In this prospective longitudinal study, serum samples from consecutive patients with histologically confirmed PCNSL were collected concurrently with magnetic resonance imaging (MRI) scans at multiple time points and were analyzed for levels of YKL-40 and MMP-9 by enzyme-linked immunosorbent assay. Marker levels were correlated to disease status and survival.

Results:

Forty-five patients with PCNSL were accrued. Median follow-up for survivors was 25 months, and 21 (47%) died during the study. A total of 230 serum samples were collected, and 93% had corresponding MRI scans. PCNSL patients without evidence of radiographic disease (29 patients, 131 samples) had significantly lower levels of serum YKL-40 and MMP-9 than patients with active tumor (n = 34 patients, 84 samples; p = 0.03 and 0.01, respectively). There was a significant inverse correlation between survival and doubling of the YKL-40 level (hazard ratio, 1.7; p = 0.01).

Interpretation:

In patients with PCNSL, serum levels of YKL-40 and MMP-9 are associated with radiographic disease status. Longitudinal increase in serum levels of YKL-40, but not MMP-9, predicts survival in patients with PCNSL. ANN NEUROL 2011

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