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Serum levels of GFAP and EGFR in primary and recurrent high-grade gliomas: correlation to tumor volume, molecular markers, and progression-free survival

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Abstract

Our aim was to study the association of two potential serum biomarkers glial fibrillary acidic protein (GFAP) and epidermal growth factor receptor (EGFR) with prognostic markers such as IDH1 mutation, tumor burden, and survival in patients with high-grade gliomas (HGG). Additionally, our objective was to evaluate the potential of serum EGFR as a surrogate marker for EGFR status in the tumor. Pre-operative serum samples were prospectively collected from patients with primary (n = 17) or recurrent (n = 10) HGG. Serum GFAP and EGFR levels were determined by ELISA and studied for correlation with molecular markers including EGFR amplification, tumor volume in contrast-enhanced T1-weighted MRI, and progression-free survival (PFS). Pre-operative serum GFAP level of ≥0.014 ng/ml was 86 % sensitive and 85 % specific for the diagnosis of glioblastoma. High GFAP was related to the lack of IDH1 mutation (P = 0.016), high Ki67 proliferation index (P < 0.001), and poor PFS (HR 5.9, CI 1.2–29.9, P = 0.032). Serum GFAP correlated with enhancing tumor volume in primary (r = 0.64 P = 0.005), but also in recurrent HGGs (r = 0.76 P = 0.011). In contrast, serum EGFR levels did not differ between HGG patients and 13 healthy controls, and were not related to EGFR status in the tumor. We conclude that high serum GFAP associates with IDH1 mutation-negative HGG, and poor PFS. Correlation with tumor burden in recurrent HGG implicates the potential of serum GFAP for detection of tumor recurrence. Our results suggest that circulating EGFR is not derived from glioma cells and cannot be used as a marker for EGFR status in the tumor.

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Acknowledgments

We thank Taina Kirjonen (Department of Physiology, University of Turku), Sinikka Kollanus and Minnamaija Lintunen (Department of Pathology, Turku University Hospital) for excellent technical assistance.

Funding

This study was funded by Cancer Society of Finland and Southwest Finland Hospital District (EVO research funding). A.K. is a Ph.D. student supported by the National Graduate School of Clinical Investigation.

Conflict of interest

The authors declare that they have no conflict of interest.

Compliance with ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Authors and Affiliations

  1. Department of Radiology, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, 20521, Turku, Finland

    Aida Kiviniemi, Riitta Parkkola & Marko Pesola

  2. Department of Pathology, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, 20521, Turku, Finland

    Maria Gardberg

  3. Department of Neurosurgery, Turku University Hospital, Hämeentie 11, 20521, Turku, Finland

    Janek Frantzén & Ville Vuorinen

  4. Department of Oncology and Radiotherapy, Turku University Hospital, Hämeentie 11, 20521, Turku, Finland

    Heikki Minn

Authors
  1. Aida Kiviniemi
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  2. Maria Gardberg
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  3. Janek Frantzén
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  4. Riitta Parkkola
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  5. Ville Vuorinen
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  6. Marko Pesola
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  7. Heikki Minn
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Correspondence to Aida Kiviniemi.

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Kiviniemi, A., Gardberg, M., Frantzén, J. et al. Serum levels of GFAP and EGFR in primary and recurrent high-grade gliomas: correlation to tumor volume, molecular markers, and progression-free survival. J Neurooncol 124, 237–245 (2015). https://doi.org/10.1007/s11060-015-1829-7

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  • DOI: https://doi.org/10.1007/s11060-015-1829-7

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