Glioblastomas in the older old.
BACKGROUND
Recent studies have identified fundamental biological differences in the effects of epidermal growth factor receptor (EGFR) amplification on survival in older versus younger patients with glioblastoma multiforme (GBM). Cell cycle labeling indices have also been found to be inordinately high in older GBM patients and may contribute to the known adverse prognosis in this cohort. However, testing has not been conducted on significant numbers of patients of very advanced age, in whom these features might be expected to emerge as even more significant factors.


OBJECTIVE
To assess EGFR amplification status and MIB-1 indices in patients with GBM who are older than 75 years.


METHODS
We identified 20 patients (female-male ratio, 11:9; 11 aged 75-79 years and 9 aged 80-87 years) and studied tumor tissue samples with immunohistochemistry for cell cycle labeling index and by fluorescence in situ hybridization for EGFR amplification. Survival data were obtained from the Colorado Tumor Registry.


RESULTS
Mean MIB-1 index was high (24.8%), but individual indices did not correlate with survival. EGFR amplification was detected in 25% of cases, with gain of chromosome 7 in all but one of the remaining patients. Ninety-five percent of patients manifested EGFR amplification and/or polysomy of chromosome 7. Heterogeneity was found within a given tumor, with 10% to 60% of cells showing gain of chromosome 7. Overall patient survival was poor (mean, 4.6 months), but was significantly longer in those with EGFR gene amplification (mean, 8.3 months; median, 10.5 months) versus those without (mean, 3.2 months; median, 2.0 months) (P = .04).


CONCLUSIONS
The presence of EGFR amplification is a significant predictor of survival time in older old patients.
Kleinschmidt-DeMasters
B K
BK
Department of Pathology, University of Colorado Health Sciences Center, Denver, CO 80262, USA. bk.demasters@uchsc.edu
Lillehei
K O
KO
Varella-Garcia
M
M
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D001932:Brain Neoplasms / Q000737:chemistry / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis / Q000737:chemistry; D005260:Female; D005784:Gene Amplification; D005909:Glioblastoma / Q000737:chemistry / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D015996:Survival Rate
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D066246:ErbB Receptors