title: Serum levels of GFAP and EGFR in primary and recurrent high-grade gliomas: correlation to tumor volume, molecular markers, and progression-free survival.
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.
authors.affiliation: Department of Radiology, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, 20521, Turku, Finland. aida.kiviniemi@utu.fi.
authors.forename: Aida
authors.initials: A
authors.lastname: Kiviniemi
authors.affiliation: Department of Pathology, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, 20521, Turku, Finland.
authors.forename: Maria
authors.initials: M
authors.lastname: Gardberg
authors.affiliation: Department of Neurosurgery, Turku University Hospital, Hämeentie 11, 20521, Turku, Finland.
authors.forename: Janek
authors.initials: J
authors.lastname: Frantzén
authors.affiliation: Department of Radiology, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, 20521, Turku, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Parkkola
authors.affiliation: Department of Neurosurgery, Turku University Hospital, Hämeentie 11, 20521, Turku, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Vuorinen
authors.affiliation: Department of Radiology, Turku University Hospital, University of Turku, Kiinamyllynkatu 4-8, 20521, Turku, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Pesola
authors.affiliation: Department of Oncology and Radiotherapy, Turku University Hospital, Hämeentie 11, 20521, Turku, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Minn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D066246:ErbB Receptors / Q000097:blood*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000097:blood*; D005910:Glioma / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology* / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D011379:Prognosis; D011446:Prospective Studies; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D005904:Glial Fibrillary Acidic Protein; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; GFAP; High-grade glioma; Prognosis; Serum biomarker; Tumor volume