Epidermal growth factor receptor variant III status defines clinically distinct subtypes of glioblastoma.
OBJECTIVE
The clinical significance of epidermal growth factor receptor variant III (EGFRvIII) expression in glioblastoma multiforme (GBM) and its relationship with other key molecular markers are not clear. We sought to evaluate the clinical significance of GBM subtypes as defined by EGFRvIII status.


METHODS
The expression of EGFRvIII was assessed by immunohistochemistry in 649 patients with newly diagnosed GBM. These data were then examined in conjunction with the expression of phospho-intermediates (in a subset of these patients) of downstream AKT and Ras pathways and YKL-40 as well as with known clinical risk factors, including the Radiation Therapy Oncology Group's recursive partitioning analysis (RTOG-RPA) class.


RESULTS
The RTOG-RPA class was highly predictive of survival in EGFRvIII-negative patients but much less predictive in EGFRvIII-positive patients. These findings were seen in both an initial test set (n = 268) and a larger validation set (n = 381). Similarly, activation of the AKT/MAPK pathways and YKL-40 positivity were predictive of poor outcome in EGFRvIII-negative patients but not in EGFRvIII-positive patients. Pair-wise combinations of markers identified EGFRvIII and YKL-40 as prognostically important. In particular, outcome in patients with EGFRvIII-negative/YKL-40-negative tumors was significantly better than the outcome in patients with the other three combinations of these two markers.


CONCLUSIONS
Established prognostic factors in GBM were not predictive of outcome in the EGFRvIII-positive subset, although this requires confirmation in independent data sets. GBMs negative for both EGFRvIII and YKL-40 show less aggressive behavior.
Pelloski
Christopher E
CE
Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Ballman
Karla V
KV
Furth
Alfred F
AF
Zhang
Li
L
Lin
E
E
Sulman
Erik P
EP
Bhat
Krishna
K
McDonald
J Matthew
JM
Yung
W K Alfred
WK
Colman
Howard
H
Woo
Shiao Y
SY
Heimberger
Amy B
AB
Suki
Dima
D
Prados
Michael D
MD
Chang
Susan M
SM
Barker
Fred G
FG
Buckner
Jan C
JC
James
C David
CD
Aldape
Kenneth
K
D054392:Adipokines; D000071451:Chitinase-3-Like Protein 1; D066246:ErbB Receptors / Q000032:analysis*; D005909:Glioblastoma / Q000737:chemistry* / Q000145:classification / Q000401:mortality; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D037102:Lectins; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012044:Regression Analysis
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; D037102:Lectins; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors