Skip to main content
Erschienen in: Journal of Neuro-Oncology 2/2016

01.01.2016 | Clinical Study

Prospective evaluation of serum glial fibrillary acidic protein (GFAP) as a diagnostic marker for glioblastoma

verfasst von: Julia Tichy, Sabrina Spechtmeyer, Michel Mittelbronn, Elke Hattingen, Johannes Rieger, Christian Senft, Christian Foerch

Erschienen in: Journal of Neuro-Oncology | Ausgabe 2/2016

Einloggen, um Zugang zu erhalten

Abstract

Glioblastoma (GBM) is the most common malignant primary brain tumor. Although clinical presentation and brain imaging might be suggestive, histopathological evaluation by means of a brain biopsy is routinely performed to establish the diagnosis. A serum marker indicative of GBM may simplify the diagnostic work-up of patients suspected to having a brain tumor. We prospectively examined 113 patients with newly diagnosed single supratentorial or infratentorial space-occupying brain lesions. Glial fibrillary acidic protein (GFAP) levels were determined from venous blood samples via a prototype ELISA assay prior to any invasive procedures. Serum levels of GFAP were correlated with histopathological findings and MRI parameters. GFAP values were significantly higher in GBM patients (n = 33) compared to all other tumors (p < 0.001). A GFAP serum concentration of ≥0.01 µg/L revealed a sensitivity of 85 % and a specificity of 70 % for differentiating GBM from other entities. By applying a GFAP cut-off point of 0.20 µg/L, specificity was maximized (99 %), but sensitivity dropped to 27 %. In GBM patients, serum GFAP values were significantly correlated with tumor volume. GBM patients with high GFAP levels showed more in vivo GFAP expression as well as more necrosis and perilesional edema compared to GBM patients having low or non-detectable GFAP levels. GFAP serum concentrations differentiated between patients with GBM and patients with cerebral mass lesions of other entities with a moderate diagnostic accuracy. Serum GFAP levels in GBM patients were positively correlated with tumor volume and histopathological tumor characteristics.
Literatur
1.
Zurück zum Zitat Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL, Burkhard C, Schuler D, Probst-Hensch NM, Maiorka PC, Baeza N, Pisani P, Yonekawa Y, Yasargil MG, Lutolf UM, Kleihues P (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64:6892–6899PubMedCrossRef Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL, Burkhard C, Schuler D, Probst-Hensch NM, Maiorka PC, Baeza N, Pisani P, Yonekawa Y, Yasargil MG, Lutolf UM, Kleihues P (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64:6892–6899PubMedCrossRef
2.
Zurück zum Zitat Okonogi N, Shirai K, Oike T, Murata K, Noda SE, Suzuki Y, Nakano T (2015) Topics in chemotherapy, molecular-targeted therapy, and immunotherapy for newly-diagnosed glioblastoma multiforme. Anticancer Res 35:1229–1235PubMed Okonogi N, Shirai K, Oike T, Murata K, Noda SE, Suzuki Y, Nakano T (2015) Topics in chemotherapy, molecular-targeted therapy, and immunotherapy for newly-diagnosed glioblastoma multiforme. Anticancer Res 35:1229–1235PubMed
3.
Zurück zum Zitat Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996PubMedCrossRef Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352:987–996PubMedCrossRef
4.
Zurück zum Zitat Eng LF (1985) Glial fibrillary acidic protein (GFAP): the major protein of glial intermediate filaments in differentiated astrocytes. J Neuroimmunol 8:203–214PubMedCrossRef Eng LF (1985) Glial fibrillary acidic protein (GFAP): the major protein of glial intermediate filaments in differentiated astrocytes. J Neuroimmunol 8:203–214PubMedCrossRef
5.
Zurück zum Zitat Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000). Neurochem Res 25:1439–1451PubMedCrossRef Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000). Neurochem Res 25:1439–1451PubMedCrossRef
6.
Zurück zum Zitat 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 116:380–384PubMedCrossRef 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 116:380–384PubMedCrossRef
7.
Zurück zum Zitat 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 120:3972–3980PubMedCrossRef 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 120:3972–3980PubMedCrossRef
8.
Zurück zum Zitat 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 130:3336–3341PubMedCrossRef 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 130:3336–3341PubMedCrossRef
9.
Zurück zum Zitat Jung CS, Unterberg AW, Hartmann C (2011) Diagnostic markers for glioblastoma. Histol Histopathol 26:1327–1341PubMed Jung CS, Unterberg AW, Hartmann C (2011) Diagnostic markers for glioblastoma. Histol Histopathol 26:1327–1341PubMed
10.
Zurück zum Zitat Diaz-Arrastia R, Wang KK, Papa L, Sorani MD, Yue JK, Puccio AM, McMahon PJ, Inoue T, Yuh EL, Lingsma HF, Maas AI, Valadka AB, Okonkwo DO, Manley GT (2014) Acute biomarkers of traumatic brain injury: relationship between plasma levels of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein. J Neurotrauma 31:19–25PubMedPubMedCentralCrossRef Diaz-Arrastia R, Wang KK, Papa L, Sorani MD, Yue JK, Puccio AM, McMahon PJ, Inoue T, Yuh EL, Lingsma HF, Maas AI, Valadka AB, Okonkwo DO, Manley GT (2014) Acute biomarkers of traumatic brain injury: relationship between plasma levels of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein. J Neurotrauma 31:19–25PubMedPubMedCentralCrossRef
11.
Zurück zum Zitat 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 (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 58:237–245PubMedCrossRef 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 (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 58:237–245PubMedCrossRef
12.
Zurück zum Zitat Nduom EK, Yang C, Merrill MJ, Zhuang Z, Lonser RR (2013) Characterization of the blood-brain barrier of metastatic and primary malignant neoplasms. J Neurosurg 119:427–433PubMedCrossRef Nduom EK, Yang C, Merrill MJ, Zhuang Z, Lonser RR (2013) Characterization of the blood-brain barrier of metastatic and primary malignant neoplasms. J Neurosurg 119:427–433PubMedCrossRef
13.
Zurück zum Zitat Yung WK, Luna M, Borit A (1985) Vimentin and glial fibrillary acidic protein in human brain tumors. J Neurooncol 3:35–38PubMed Yung WK, Luna M, Borit A (1985) Vimentin and glial fibrillary acidic protein in human brain tumors. J Neurooncol 3:35–38PubMed
14.
Zurück zum Zitat Lyubimova NV, Toms MG, Popova EE, Bondarenko YV, Krat VB, Kushlinskii NE (2011) Neurospecific proteins in the serum of patients with brain tumors. Bull Exp Biol Med 150:732–734PubMedCrossRef Lyubimova NV, Toms MG, Popova EE, Bondarenko YV, Krat VB, Kushlinskii NE (2011) Neurospecific proteins in the serum of patients with brain tumors. Bull Exp Biol Med 150:732–734PubMedCrossRef
15.
Zurück zum Zitat Larsson IM, Wallin E, Kristofferzon ML, Niessner M, Zetterberg H, Rubertsson S (2014) Post-cardiac arrest serum levels of glial fibrillary acidic protein for predicting neurological outcome. Resuscitation 85:1654–1661PubMedCrossRef Larsson IM, Wallin E, Kristofferzon ML, Niessner M, Zetterberg H, Rubertsson S (2014) Post-cardiac arrest serum levels of glial fibrillary acidic protein for predicting neurological outcome. Resuscitation 85:1654–1661PubMedCrossRef
16.
Zurück zum Zitat Mayer CA, Brunkhorst R, Niessner M, Pfeilschifter W, Steinmetz H, Foerch C (2013) Blood levels of glial fibrillary acidic protein (GFAP) in patients with neurological diseases. PLoS One 8:e62101PubMedPubMedCentralCrossRef Mayer CA, Brunkhorst R, Niessner M, Pfeilschifter W, Steinmetz H, Foerch C (2013) Blood levels of glial fibrillary acidic protein (GFAP) in patients with neurological diseases. PLoS One 8:e62101PubMedPubMedCentralCrossRef
17.
Zurück zum Zitat Kleihues P, Burger PC, Scheithauer BW (1993) The new WHO classification of brain tumours. Brain Pathol 3:255–268PubMedCrossRef Kleihues P, Burger PC, Scheithauer BW (1993) The new WHO classification of brain tumours. Brain Pathol 3:255–268PubMedCrossRef
18.
Zurück zum Zitat Harter PN, Bunz B, Dietz K, Hoffmann K, Meyermann R, Mittelbronn M (2010) Spatio-temporal deleted in colorectal cancer (DCC) and netrin-1 expression in human foetal brain development. Neuropathol Appl Neurobiol 36:623–635PubMedCrossRef Harter PN, Bunz B, Dietz K, Hoffmann K, Meyermann R, Mittelbronn M (2010) Spatio-temporal deleted in colorectal cancer (DCC) and netrin-1 expression in human foetal brain development. Neuropathol Appl Neurobiol 36:623–635PubMedCrossRef
19.
Zurück zum Zitat Wang K, Wang YY, Ma J, Wang JF, Li SW, Jiang T, Dai JP (2014) Prognostic value of MGMT promoter methylation and TP53 mutation in glioblastomas depends on IDH1 mutation. Asian Pac J Cancer Prev 15:10893–10898PubMedCrossRef Wang K, Wang YY, Ma J, Wang JF, Li SW, Jiang T, Dai JP (2014) Prognostic value of MGMT promoter methylation and TP53 mutation in glioblastomas depends on IDH1 mutation. Asian Pac J Cancer Prev 15:10893–10898PubMedCrossRef
20.
Zurück zum Zitat Weller M, Tabatabai G, Kastner B, Felsberg J, Steinbach JP, Wick A, Schnell O, Hau P, Herrlinger U, Sabel MC, Wirsching HG, Ketter R, Bahr O, Platten M, Tonn JC, Schlegel U, Marosi C, Goldbrunner R, Stupp R, Homicsko K, Pichler J, Nikkhah G, Meixensberger J, Vajkoczy P, Kollias S, Husing J, Reifenberger G, Wick W (2015) MGMT promoter methylation is a strong prognostic biomarker for benefit from dose-intensified temozolomide rechallenge in progressive glioblastoma: the DIRECTOR trial. Clin Cancer Res 21(9):2057–2064PubMedCrossRef Weller M, Tabatabai G, Kastner B, Felsberg J, Steinbach JP, Wick A, Schnell O, Hau P, Herrlinger U, Sabel MC, Wirsching HG, Ketter R, Bahr O, Platten M, Tonn JC, Schlegel U, Marosi C, Goldbrunner R, Stupp R, Homicsko K, Pichler J, Nikkhah G, Meixensberger J, Vajkoczy P, Kollias S, Husing J, Reifenberger G, Wick W (2015) MGMT promoter methylation is a strong prognostic biomarker for benefit from dose-intensified temozolomide rechallenge in progressive glioblastoma: the DIRECTOR trial. Clin Cancer Res 21(9):2057–2064PubMedCrossRef
21.
Zurück zum Zitat Weise LM, Harter PN, Eibach S, Braczynski AK, Dunst M, Rieger J, Bahr O, Hattingen E, Steinbach JP, Plate KH, Seifert V, Mittelbronn M (2014) Confounding factors in diagnostics of MGMT promoter methylation status in glioblastomas in stereotactic biopsies. Stereotact Funct Neurosurg 92:129–139PubMed Weise LM, Harter PN, Eibach S, Braczynski AK, Dunst M, Rieger J, Bahr O, Hattingen E, Steinbach JP, Plate KH, Seifert V, Mittelbronn M (2014) Confounding factors in diagnostics of MGMT promoter methylation status in glioblastomas in stereotactic biopsies. Stereotact Funct Neurosurg 92:129–139PubMed
22.
Zurück zum Zitat Kothari RU, Brott T, Broderick JP, Barsan WG, Sauerbeck LR, Zuccarello M, Khoury J (1996) The ABCs of measuring intracerebral hemorrhage volumes. Stroke 27:1304–1305PubMedCrossRef Kothari RU, Brott T, Broderick JP, Barsan WG, Sauerbeck LR, Zuccarello M, Khoury J (1996) The ABCs of measuring intracerebral hemorrhage volumes. Stroke 27:1304–1305PubMedCrossRef
23.
Zurück zum Zitat Papa L, Silvestri S, Brophy GM, Giordano P, Falk JL, Braga CF, Tan CN, Ameli NJ, Demery JA, Dixit NK, Mendes ME, Hayes RL, Wang KK, Robertson CS (2014) GFAP out-performs S100beta in detecting traumatic intracranial lesions on computed tomography in trauma patients with mild traumatic brain injury and those with extracranial lesions. J Neurotrauma 31:1815–1822PubMedPubMedCentralCrossRef Papa L, Silvestri S, Brophy GM, Giordano P, Falk JL, Braga CF, Tan CN, Ameli NJ, Demery JA, Dixit NK, Mendes ME, Hayes RL, Wang KK, Robertson CS (2014) GFAP out-performs S100beta in detecting traumatic intracranial lesions on computed tomography in trauma patients with mild traumatic brain injury and those with extracranial lesions. J Neurotrauma 31:1815–1822PubMedPubMedCentralCrossRef
24.
Zurück zum Zitat Petzold A (2015) Glial fibrillary acidic protein is a body fluid biomarker for glial pathology in human disease. Brain Res 1600:17–31PubMedCrossRef Petzold A (2015) Glial fibrillary acidic protein is a body fluid biomarker for glial pathology in human disease. Brain Res 1600:17–31PubMedCrossRef
25.
Zurück zum Zitat Lyubimova NV, Toms MG, Fu RG, Bondarenko YV (2013) Biochemical markers of brain tumours. Klin Lab Diagn 71–72:40–72 Lyubimova NV, Toms MG, Fu RG, Bondarenko YV (2013) Biochemical markers of brain tumours. Klin Lab Diagn 71–72:40–72
26.
Zurück zum Zitat Wilhelmsson U, Eliasson C, Bjerkvig R, Pekny M (2003) Loss of GFAP expression in high-grade astrocytomas does not contribute to tumor development or progression. Oncogene 22:3407–3411PubMedCrossRef Wilhelmsson U, Eliasson C, Bjerkvig R, Pekny M (2003) Loss of GFAP expression in high-grade astrocytomas does not contribute to tumor development or progression. Oncogene 22:3407–3411PubMedCrossRef
27.
Zurück zum Zitat Brunkhorst R, Pfeilschifter W, Foerch C (2010) Astroglial proteins as diagnostic markers of acute intracerebral hemorrhage-pathophysiological background and clinical findings. Transl Stroke Res 1:246–251PubMedCrossRef Brunkhorst R, Pfeilschifter W, Foerch C (2010) Astroglial proteins as diagnostic markers of acute intracerebral hemorrhage-pathophysiological background and clinical findings. Transl Stroke Res 1:246–251PubMedCrossRef
28.
Zurück zum Zitat Noreen F, Roosli M, Gaj P, Pietrzak J, Weis S, Urfer P, Regula J, Schar P, Truninger K (2014) Modulation of age- and cancer-associated DNA methylation change in the healthy colon by aspirin and lifestyle. J Natl Cancer Inst 106(7):dju161PubMedPubMedCentralCrossRef Noreen F, Roosli M, Gaj P, Pietrzak J, Weis S, Urfer P, Regula J, Schar P, Truninger K (2014) Modulation of age- and cancer-associated DNA methylation change in the healthy colon by aspirin and lifestyle. J Natl Cancer Inst 106(7):dju161PubMedPubMedCentralCrossRef
29.
Zurück zum Zitat 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 124:237–245PubMedCrossRef 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 124:237–245PubMedCrossRef
Metadaten
Titel
Prospective evaluation of serum glial fibrillary acidic protein (GFAP) as a diagnostic marker for glioblastoma
verfasst von
Julia Tichy
Sabrina Spechtmeyer
Michel Mittelbronn
Elke Hattingen
Johannes Rieger
Christian Senft
Christian Foerch
Publikationsdatum
01.01.2016
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 2/2016
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-015-1978-8

Weitere Artikel der Ausgabe 2/2016

Journal of Neuro-Oncology 2/2016 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Frühe Alzheimertherapie lohnt sich

25.04.2024 AAN-Jahrestagung 2024 Nachrichten

Ist die Tau-Last noch gering, scheint der Vorteil von Lecanemab besonders groß zu sein. Und beginnen Erkrankte verzögert mit der Behandlung, erreichen sie nicht mehr die kognitive Leistung wie bei einem früheren Start. Darauf deuten neue Analysen der Phase-3-Studie Clarity AD.

Viel Bewegung in der Parkinsonforschung

25.04.2024 Parkinson-Krankheit Nachrichten

Neue arznei- und zellbasierte Ansätze, Frühdiagnose mit Bewegungssensoren, Rückenmarkstimulation gegen Gehblockaden – in der Parkinsonforschung tut sich einiges. Auf dem Deutschen Parkinsonkongress ging es auch viel um technische Innovationen.

Demenzkranke durch Antipsychotika vielfach gefährdet

23.04.2024 Demenz Nachrichten

Wenn Demenzkranke aufgrund von Symptomen wie Agitation oder Aggressivität mit Antipsychotika behandelt werden, sind damit offenbar noch mehr Risiken verbunden als bislang angenommen.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.