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Serum concentrations of glial fibrillary acidic protein (GFAP) do not indicate tumor recurrence in patients with glioblastoma

  • Clinical Study
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Abstract

Recent studies identified serum concentrations of the astroglial protein glial fibrillary acidic protein (GFAP) to be indicative of glioblastoma (GBM) in patients with newly diagnosed space occupying cerebral mass lesions. Until now, no data is available whether GFAP serum concentrations decrease after first therapy and whether GFAP may be used as a predictor of survival and an indicator of tumor recurrence. In this prospective study, we included 44 patients with a single space occupying cerebral mass lesion suspicious for GBM. GBM was histopathologically proven in 33 cases. After initial therapy, patients were followed up until tumor recurrence (defined according to the RANO criteria) or death (maximum observation period 78 weeks). Blood was sampled on a regular basis, and GFAP serum levels were determined using an immunofluorescence assay. Prior to any intervention, 14 of the 33 GBM patients had elevated GFAP serum concentrations (median 0.25 µg/L, interquartile range 0.13–0.53), whereas only one out of 11 patients having other tumor entities revealed a slightly increased GFAP serum level (0.06 µg/L). Following surgery (i.e., biopsy, full or partial resection), all initially GFAP positive GBM patients showed decreased serum concentrations. During the follow-up period, we found a minimal GFAP increase in one patient only (0.04 µg/L; week 52), although 23 out of 31 available GBM patients developed tumor progression or died. No difference was found regarding the survival rate and the time to tumor recurrence between initially GFAP positive and GFAP negative GBM patients. In GBM patients, initially elevated GFAP serum concentrations decrease after the first diagnostic or therapeutic intervention. GFAP was not predictive for tumor recurrence.

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Abbreviations

Approx.:

Approximately

CCNU:

Lomustine

CSF:

Cerebrospinal fluid

CNS:

Central nervous system

GBM:

Glioblastoma

GFAP:

Glial fibrillary acidic protein

Gy:

Gray

FLAIR:

Fluid attenuated inversion recovery

IDH1:

Isocitrate dehydrogenase 1

MGMT:

O-6-Methylguanine-DNA methyltransferase

MRI:

Magnet resonance imaging

OP:

Operation

PD:

Progressive disease

PNET:

Primitive neuroectodermal tumor

RANO:

Response assessment in neuro-oncology

TMZ:

Temozolomide

WHO:

World Health Organization

References

  1. Bignami A, Eng LF, Dahl D, Uyeda CT (1972) Localization of the glial fibrillary acidic protein in astrocytes by immunofluorescence. Brain Res 43:429–435

    Article  CAS  PubMed  Google Scholar 

  2. Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000). Neurochem Res 25:1439–1451

    Article  CAS  PubMed  Google Scholar 

  3. Brunkhorst R, Pfeilschifter W, Foerch C (2010) Astroglial proteins as diagnostic markers of acute intracerebral hemorrhage-pathophysiological background and clinical findings. Transl Stroke Res 1:246–251. doi:10.1007/s12975-010-0040-6

    Article  CAS  PubMed  Google Scholar 

  4. Mondello S, Papa L, Buki A, Bullock MR, Czeiter E, Tortella FC, Wang KK, Hayes RL (2011) Neuronal and glial markers are differently associated with computed tomography findings and outcome in patients with severe traumatic brain injury: a case control study. Crit Care 15:R156. doi:10.1186/cc10286

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lumpkins KM, Bochicchio GV, Keledjian K, Simard JM, McCunn M, Scalea T (2008) Glial fibrillary acidic protein is highly correlated with brain injury. J Trauma 65: 778–782. doi:10.1097/TA.0b013e318185db2d (discussion 782–774)

    Article  CAS  PubMed  Google Scholar 

  6. Luger S, Witsch J, Dietz A, Hamann GF, Minnerup J, Schneider H, Sitzer M, Wartenberg KE, Niessner M, Foerch C, BE FAST II and the IGNITE Study Groups (2017) Glial fibrillary acidic protein serum levels distinguish between intracerebral hemorrhage and cerebral ischemia in the early phase of stroke. Clin Chem 63:377–385. doi:10.1373/clinchem.2016.263335

    Article  CAS  PubMed  Google Scholar 

  7. Foerch C, Niessner M, Back T, Bauerle M, De Marchis GM, Ferbert A, Grehl H, Hamann GF, Jacobs A, Kastrup A, Klimpe S, Palm F, Thomalla G, Worthmann H, Sitzer M, Group BFS (2012) Diagnostic accuracy of plasma glial fibrillary acidic protein for differentiating intracerebral hemorrhage and cerebral ischemia in patients with symptoms of acute stroke. Clin Chem 58:237–245. doi:10.1373/clinchem.2011.172676

    Article  CAS  PubMed  Google Scholar 

  8. Tichy J, Spechtmeyer S, Mittelbronn M, Hattingen E, Rieger J, Senft C, Foerch C (2016) Prospective evaluation of serum glial fibrillary acidic protein (GFAP) as a diagnostic marker for glioblastoma. J Neurooncol 126:361–369. doi:10.1007/s11060-015-1978-8

    Article  CAS  PubMed  Google Scholar 

  9. Jung CS, Foerch C, Schanzer A, Heck A, Plate KH, Seifert V, Steinmetz H, Raabe A, Sitzer M (2007) Serum GFAP is a diagnostic marker for glioblastoma multiforme. Brain 130:3336–3341. doi:10.1093/brain/awm263

    Article  CAS  PubMed  Google Scholar 

  10. Gallego Perez-Larraya J, Paris S, Idbaih A, Dehais C, Laigle-Donadey F, Navarro S, Capelle L, Mokhtari K, Marie Y, Sanson M, Hoang-Xuan K, Delattre JY, Mallet A (2014) Diagnostic and prognostic value of preoperative combined GFAP, IGFBP-2, and YKL-40 plasma levels in patients with glioblastoma. Cancer 120:3972–3980. doi:10.1002/cncr.28949

    Article  CAS  PubMed  Google Scholar 

  11. Brommeland T, Rosengren L, Fridlund S, Hennig R, Isaksen V (2007) Serum levels of glial fibrillary acidic protein correlate to tumour volume of high-grade gliomas. Acta Neurol Scand 116:380–384. doi:10.1111/j.1600-0404.2007.00889.x

    Article  CAS  PubMed  Google Scholar 

  12. Finn MA, Blumenthal DT, Salzman KL, Jensen RL (2007) Transient postictal MRI changes in patients with brain tumors may mimic disease progression. Surg Neurol 67: 246–250. doi:10.1016/j.surneu.2006.04.015 (discussion 250)

    Article  PubMed  Google Scholar 

  13. Kumar AJ, Leeds NE, Fuller GN, Van Tassel P, Maor MH, Sawaya RE, Levin VA (2000) Malignant gliomas: MR imaging spectrum of radiation therapy- and chemotherapy-induced necrosis of the brain after treatment. Radiology 217:377–384. doi:10.1148/radiology.217.2.r00nv36377

    Article  CAS  PubMed  Google Scholar 

  14. Hygino da Cruz LC Jr, Rodriguez I, Domingues RC, Gasparetto EL, Sorensen AG (2011) Pseudoprogression and pseudoresponse: imaging challenges in the assessment of posttreatment glioma. AJNR Am J Neuroradiol 32:1978–1985. doi:10.3174/ajnr.A2397

    Article  PubMed  Google Scholar 

  15. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB, Tsien C, Mikkelsen T, Wong ET, Chamberlain MC, Stupp R, Lamborn KR, Vogelbaum MA, van den Bent MJ, Chang SM (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972. doi:10.1200/JCO.2009.26.3541

    Article  PubMed  Google Scholar 

  16. Kiviniemi A, Gardberg M, Frantzen J, Parkkola R, Vuorinen V, Pesola M, Minn H (2015) 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. doi:10.1007/s11060-015-1829-7

    Article  CAS  PubMed  Google Scholar 

  17. Husain H, Savage W, Grossman SA, Ye X, Burger PC, Everett A, Bettegowda C, Diaz LA Jr, Blair C, Romans KE, Holdhoff M (2012) Pre- and post-operative plasma glial fibrillary acidic protein levels in patients with newly diagnosed gliomas. J Neurooncol 109:123–127. doi:10.1007/s11060-012-0874-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Gurses C, Ekizoglu O, Orhan N, Ustek D, Arican N, Ahishali B, Elmas I, Kucuk M, Bilgic B, Kemikler G, Kalayci R, Karadeniz A, Kaya M (2009) Levetiracetam decreases the seizure activity and blood-brain barrier permeability in pentylenetetrazole-kindled rats with cortical dysplasia. Brain Res 1281:71–83. doi:10.1016/j.brainres.2009.05.033

    Article  CAS  PubMed  Google Scholar 

  19. Ostergaard L, Hochberg FH, Rabinov JD, Sorensen AG, Lev M, Kim L, Weisskoff RM, Gonzalez RG, Gyldensted C, Rosen BR (1999) Early changes measured by magnetic resonance imaging in cerebral blood flow, blood volume, and blood-brain barrier permeability following dexamethasone treatment in patients with brain tumors. J Neurosurg 90:300–305. doi:10.3171/jns.1999.90.2.0300

    Article  CAS  PubMed  Google Scholar 

  20. Kim JH, Bae Kim Y, Han JH, Cho KG, Kim SH, Sheen SS, Lee HW, Jeong SY, Kim BY, Lee KB (2012) Pathologic diagnosis of recurrent glioblastoma: morphologic, immunohistochemical, and molecular analysis of 20 paired cases. Am J Surg Pathol 36:620–628. doi:10.1097/PAS.0b013e318246040c

    Article  PubMed  Google Scholar 

  21. Lacroix M, Abi-Said D, Fourney DR, Gokaslan ZL, Shi W, DeMonte F, Lang FF, McCutcheon IE, Hassenbusch SJ, Holland E, Hess K, Michael C, Miller D, Sawaya R (2001) A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95:190–198. doi:10.3171/jns.2001.95.2.0190

    Article  CAS  PubMed  Google Scholar 

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Author notes

  1. Julia Tichy and Christian Foerch have contributed equally.

Authors and Affiliations

  1. Department of Neurology, Goethe University, Schleusenweg 2-16, 60528, Frankfurt am Main, Germany

    Julia-Mareen Vietheer, Julia Tichy & Christian Foerch

  2. Department of Neuro-Oncology, Goethe University, Frankfurt am Main, Germany

    Johannes Rieger & Julia Tichy

  3. Department of Neurology & Stroke, Hertie Institute for Clinical Brain Research, Eberhard-Karls University Tübingen, Tübingen, Germany

    Johannes Rieger

  4. Institute of Neuroradiology, Goethe University, Frankfurt am Main, Germany

    Marlies Wagner

  5. Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany

    Christian Senft

Authors
  1. Julia-Mareen Vietheer
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  2. Johannes Rieger
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  3. Marlies Wagner
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  4. Christian Senft
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  5. Julia Tichy
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  6. Christian Foerch
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Contributions

Conceived and designed the experiments: JV, JT, CF. Performed the experiments: JV, MW. Analyzed the data: JV, JT, JR, CF. Contributed reagents, materials, financial support: CF. Wrote the paper: JV, JT, JR, CF. Supervisor of the study: CF. Corrected and approved the final version of the manuscript: all authors.

Corresponding author

Correspondence to Julia Tichy.

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Vietheer, JM., Rieger, J., Wagner, M. et al. Serum concentrations of glial fibrillary acidic protein (GFAP) do not indicate tumor recurrence in patients with glioblastoma. J Neurooncol 135, 193–199 (2017). https://doi.org/10.1007/s11060-017-2565-y

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  • DOI: https://doi.org/10.1007/s11060-017-2565-y

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