EGFR overexpression and radiation response in glioblastoma multiforme.
OBJECTIVE
Recent studies have suggested relative radioresistance in glioblastoma multiforme (GM) tumors in older patients, consistent with their shorter survival. Two common molecular genetic abnormalities in GM are age related: epidermal growth factor receptor (EGFR) overexpression in older patients and p53 mutations in younger patients. We tested whether these abnormalities correlated with clinical heterogeneity in GM response to radiation treatment.


METHODS
Radiographically assessed radiation response (5-level scale) was correlated with EGFR immunoreactivity, p53 immunoreactivity, and p53 exon 5-8 mutation status in 170 GM patients treated using 2 prospective clinical protocols. Spearman rank correlation and proportional-odds ordinal regression were used for univariate and multivariate analysis.


RESULTS
Positive EGFR immunoreactivity predicted poor radiographically assessed radiation response (p = 0.046). Thirty-three percent of tumors with no EGFR immunoreactivity had good radiation responses (>50% reduction in tumor size by CT or MRI), compared to 18% of tumors with intermediate EGFR staining and 9% of tumors with strong staining. There was no significant relationship between p53 immunoreactivity or mutation status and radiation response. Significant relationships were noted between EGFR score and older age and between p53 score or mutation status and younger age.


CONCLUSIONS
The observed relative radioresistance of some GMs is associated with overexpression of EGFR.
Barker
F G
FG
Department of Neurological Surgery, Neuro-Oncology Service and Brain Tumor Research Center, University of California, San Francisco, California, USA. barker@helix.mgh.harvard.edu
Simmons
M L
ML
Chang
S M
SM
Prados
M D
MD
Larson
D A
DA
Sneed
P K
PK
Wara
W M
WM
Berger
M S
MS
Chen
P
P
Israel
M A
MA
Aldape
K D
KD
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000704:Analysis of Variance; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D016017:Odds Ratio; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D012044:Regression Analysis; D015173:Supratentorial Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy*
D009363:Neoplasm Proteins; D066246:ErbB Receptors