Prognostic relevance of epidermal growth factor receptor (EGF-R) and c-neu/erbB2 expression in glioblastomas (GBMs).
Seventeen untreated primary adult glioblastomas were analyzed using immunocytochemistry for the expression of EGF-R, c-neu/erbB2, TGF-alpha, and phosphotyrosine. Patients were divided by median survival into long-term or short-term survivors (LTS, N = 10, median > 4 years; versus STS, N = 7, median 61 weeks). There were no significant differences between the two groups in terms of age, extent of resection, post-operative Karnofsky status, or treatment. Diagnostic sections from each tumor were stained with antibodies to EGF-R, c-neu/erbB2, TGF-alpha and phosphotyrosine. Double-labelling for TGF-alpha and EGF-R was also performed. All 10/10 LTS were considered to be EGF-R negative/scant, while 4/7 STS were EGF-R positive. EGF-R negativity significantly correlated with long-term survival. The differences in c-neu/erbB2 expression did not reach significance. However, 4/7 STS were positive for both proteins and 76% of the 17 cases were either double negative or positive for EGF-R and c-neu/erbB2. TGF-alpha and phosphotyrosine were frequently expressed, but neither were prognostic. Recurrent tumors were studied in 7 STS. EGF-R expression was increased in 4/7 of these cases and c-neu/erbB2 was increased in all 7 cases, compared to the pretreatment baselines. Increased expression of these proteins in glioblastomas may be associated with aggressive clinical behavior and treatment resistance.
Hiesiger
E M
EM
Department of Neurology, New York University Medical Center, New York 10016.
Hayes
R L
RL
Pierz
D M
DM
Budzilovich
G N
GN
D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D066246:ErbB Receptors / Q000032:analysis*; D005909:Glioblastoma / Q000097:blood* / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D019000:Phosphotyrosine; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D018719:Erb-b2 Receptor Tyrosine Kinases; D015996:Survival Rate; D016211:Transforming Growth Factor alpha / Q000032:analysis*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D019000:Phosphotyrosine; D011518:Proto-Oncogene Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha; D014443:Tyrosine