Increased expression of EphA7 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients.
BACKGROUND
Malignant gliomas are lethal cancers, highly dependent on angiogenesis and treatment options and prognosis still remain poor for patients with recurrent glioblastoma multiforme (GBM). Ephs and ephrins have many well-defined functions during embryonic development of central nervous system such as axon mapping, neural crest cell migration, hindbrain segmentation and synapse formation as well as physiological and abnormal angiogenesis. Accumulating evidence indicates that Eph and ephrins are frequently overexpressed in different tumor types including GBM. However, their role in tumorigenesis remains controversial, as both tumor growth promoter and suppressor potential have been ascribed to Eph and ephrins while the function of EphA7 in GBM pathogenesis remains largely unknown.


METHODS
In this study, we investigated the immunohistochemical expression of EphA7 in a series of 32 primary and recurrent GBM and correlated it with clinical pathological parameters and patient outcome. In addition, intratumor microvascular density (MVD) was quantified by immunostaining for endothelial cell marker von Willebrand factor (vWF).


RESULTS
Overexpression of EphA7 protein was predictive of the adverse outcome in GBM patients, independent of MVD expression (p = 0.02). Moreover, high density of MVD as well as higher EphA7 expression predicted the disease outcome more accurately than EphA7 variable alone (p = 0.01). There was no correlation between MVD and overall survival or recurrence-free survival (p > 0.05). However, a statistically significant correlation between lower MVD and tumor recurrence was observed (p = 0.003).


CONCLUSIONS
The immunohistochemical assessment of tissue EphA7 provides important prognostic information in GBM and would justify its use as surrogate marker to screen patients for tyrosine kinase inhibitor therapy.
Wang
Lin-Fang
LF
Department of Radiotherapy and Radiation Oncology, Philipps-University Marburg, Baldingerstr, D-35043 Marburg, Germany. wang@staff.uni-marburg.de
Fokas
Emmanouil
E
Juricko
Janko
J
You
An
A
Rose
Frank
F
Pagenstecher
Axel
A
Engenhart-Cabillic
Rita
R
An
Han-Xiang
HX
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D036141:Receptor, EphA7 / Q000096:biosynthesis*; D012008:Recurrence; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000378:metabolism
D014841:von Willebrand Factor; D036141:Receptor, EphA7