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Immunohistochemical
detection of EGFRvIII and prognostic significance in patients with malignant
glioma enrolled in NCCTG clinical trials
J. C. Buckner, K. D. Aldape, K. Ballman, B. W. Scheithauer, P. C. Burger, C.
Giannini, P. L. Schaefer, R. B. Jenkins, C. D. James
Mayo Clinic College of Medicine, Rochester, MN; MD Anderson,
Houston, TX; Johns Hopkins University School of Medicine, Baltimore, MD; Toledo
Community CCOP, Toledo, OH
Background. Egf receptor variant III (vIII) is an aberrant tyrosine
kinase that lacks a substantial portion of full length Egf receptor’s
extracellular domain, and has been suggested as being exclusively expressed in
human glioblastoma.
Little is known, however, with regard to the prognostic significance vIII
expression in glioblastoma.
Methods. To assess associations between vIII expression and malignant
glioma classification, as well to asses its prognostic significance, tumor
tissues were collected from malignant glioma patients enrolled in 10 prospective
clinical trials, and these were examined for vIII expression by
immunohistochemistry.
Of the 168 evaluable specimens, 63 were classified as being of grade III
malignancy (56 anaplastic astrocytomas and 7 anaplastic oligoastrocytomas), and
105 as grade IV tumors (glioblastoma multiforme), based on WHO criteria.
All patients received radiation therapy and nitrosourea-based adjuvant
chemotherapy without any difference in outcome related to treatment.
Results. Incidence of vIII expression and associations with malignancy
grade are as indicated in the table below.
vIII expression was determined as being significantly associated with reduced
survival in grade III tumors (0.0016), but not in patients with GBM
(0.84).
Patient age and performance status were determined as significant prognostic
indicators for each group of tumors.
Conclusions. Since the average survival of vIII-positive anaplastic
glioma patients was only 7.2 months, as compared with 33.0 months for their
vIII-negative counterparts, our results support vIII IHC as being a useful test
for identifying anaplastic gliomas whose clinical behavior is consistent with
that of GBM.
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Grade III (N=63)
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Grade IV (N=105)
|
|
N
|
Med surv. mos
|
12-mo survival (95% CI)
|
p-value
|
N
|
Med surv. mos
|
12-mo survival (95% CI)
|
p-value
|
|
EGFRvIII
Negative
Positive
|
54
9
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33.0
7.2
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72 (61 to 85)
22 (7 to 75)
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0.0016
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83
22
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12.6
12.4
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54 (45 to 66)
59 (42 to 84)
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0.84
|
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Age
< 40
40-60
> 60
|
27
22
14
|
66.0
24.9
4.6
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85 (73 to 100)
77 (62 to 97)
7 (1 to 47)
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<0.0001
|
10
55
40
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12.6
14.8
9.2
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70 (47 to 100)
69 (58 to 82)
33 (21 to 51)
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0.0026
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|
Per. Status
0
1
2
3
|
16
26
14
6
|
33.0
39.3
5.1
6.8
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69 (49 to 96)
81 (67 to 97)
42 (23 to 79)
33 (11 to 100)
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0.010
|
24
53
16
11
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15.8
12.6
9.9
8.9
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75 (60 to 95)
57 (45 to 72)
44 (25 to 76)
27 (10 to 72)
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0.003
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Ext. Resec.
BX
GTR
STR
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26
10
27
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10.2
24.9
49.1
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52 (35 to 77)
100
90 (78 to 100)
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0.31
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23
24
58
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13.1
12.4
12.4
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46 (31 to 70)
80 (59 to 100)
78 (64 to 95)
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0.81
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Copyright 2004 American Society of Clinical Oncology All rights
reserved worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-003918,00.asp
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