Download Expression of the Genes Encoding Myelin Basic Protein and

Vol. 3, 799-804,
May
1997
Clinical
Expression
of the Genes
Proteolipid
Protein
John
Golflnos,2
G.
Stephen
W.
Conrad
Ballecer,
Sylvia
Coons,
Encoding
in Human
Myelin
Malignant
had
median
Adrienne
than
(grade
Division of Neurosurgery
[J. 0. G.], Neuro-Oncology
Research
[S. A. N., C. B., A. C. S.], and Division of Neuropathology
[S. W. C.],
Barrow Neurological
Institute of St. Joseph’s Hospital and Medical
Center, Phoenix, Arizona 85013, and National Institutes
of Health,
National Institute of Diabetes and Digestive
and Kidney Disorders,
Phoenix, Arizona [R. A. N.]
a 75%
5-year
rates
of patients
survival
less
C. Scheck3
1 year
for
reliable
tissue-specific
been
found;
thus,
these
tumors
rely
Furthermore,
ABSTRACT
trocytoma.
Pathological
differentiation
of oligodendroglioma
and
mixed oligoastrocytoma
from astrocytoma
is difficult,
relying on morphological
characteristics
due to the lack of reliable immunohistochemical
stains.
Oligodendrocytes,
the
presumed
cell of origin of oligodendrogliomas,
highly express
the genes encoding
myelin basic protein
(MBP)
and
proteolipid
protein
(PLP).
We analyzed
the expression
of
these genes to determine
whether
they might be useful molecular
markers
of oligodendrocytic
tumors.
MBP and PLP
were highly expressed
in all oligodendrogliomas
and minimally expressed
in glioblastomas
multiforme.
MBP
was
complicated
on
in mixed
oligoastrocytomas,
whereas
PLP
classification
statistically
as a useful
significant.
Expression
molecular
marker
of these
for some
genes
may
subtypes
(5).
inherent
serve
of human
term
malignant
survival
of these
from
gliomas
Current
(1);
tumors
tumor
accepted
(2).
The
subtypes
major
oligodendroglioma.
cytomas.
oligodendrocyte
In a recent
solid
scheme
review,
tumors
with
cases
of long-
for different
survival
of a reliable
for histopathological
glioma
are
and
patients
the
are
are less
individually
reviewed
beginning
of the
review
with
tumors
low-grade
of
than
study,
to 69%.
Neurological
gliomas
using
the
tumors
more
reclassified
ods
for identifying
of the
lack
and
genetic
highly
of myelin
classified
express
sheaths
and
80-90%
of the proteins
pre-
Therefore,
we hypothesized
may
serve
as molecular
from
oligodendrocytic
astro-
oligoden-
by these
mas
(grades
difference
Received
9/20/96; revised 12/23/96; accepted
1/31/97.
The costs of publication
of this article were defrayed
in part by the
payment of page charges. This article must therefore be hereby marked
advertisement
in accordance
with 18 U.S.C. Section
1734 solely to
indicate this fact.
I This
work was supported
by NIH Grant CA 50931.
2 Present
address: Department
of Neurosurgery,
New York University
Medical Center, 530 First Avenue, New York, NY 10016.
3 To whom requests
for reprints should be addressed,
at Neuro-Oncology Research,
Barrow Neurological
Institute of St. Joseph’s
Hospital
and Medical Center, 350 West Thomas Road, Phoenix, AZ 85013.
PLP
marker
2 and
in the
The abbreviations
lipid protein.
4
the
and
used are: MBP,
to be
prognosis,
myelin
for
myelin
(1 1).
of these
genes
arising
of tissues
and
a statistically
This
The
account
of tumors
analysis
genes
is likely
patient
(7-10).
system
oligoastrocytomas,
of the
methOligoden-
PLP)
expression
Our
mixed
for the elaboration
markers
of gliomas.
genes
type,
methand
system
nervous
4) demonstrates
subtypes
of these
for tumor
(MB!”
types.
expression
44 (16%)
types.
nervous
biological
cell
315
criteria.
biological
tumor
responsible
that
of
neuropathological
of these
genes
mixed
in different
expression
histological
to use molecular
in central
oligodendrogliomas,
at the
set
or oligoastrocytomas.
the central
encoded
after
defined,
as astrocytomas,
the genes
within
were
At the
however,
oligodendrogliomas
markers
State
and grade.
a second
of objective
grading
Ohio
neuropathologists
defined
the
samples
52%;
reviewed
we sought
to identify
drocytes
two
in
from
to be better
as oligodendrogliomas
oligoastrocytomas,
ods
was
precisely
originally
were
impordifficulty
and
type
of
underscored
tumor
criteria
The
The
Clinic,
tumor
Institute
relative
was
and forty-four
histological
rose
Barrow
contain
is uncer-
tumor.
tumors
concordance
allowed
that
The prognosis
neuropathologists
to determine
as-
is further
tumors
as is the
the Mayo
is not
from
tumors
the
of glial
hundred
this
oligoastrocytomas,
by four
Institute,
(6). Two
protein,
elements.
within
(4).
gliofibrillary
of these
mixed
types
proteins
grading
astrocytoma
common
a
subtypes
of patient
by the lack
Oligodendrogliomas
origin
few
Predictions
is hampered
of
brain
produces
the prognosis
widely.
histopathology
universally
are
therapy
however,
can vary
and
sumed
Neurological
University
acid
alone
and
oligodendroglioma
are debated,
tissue
conducted
Because
prognosis.
criteria
two
study
Barrow
INTRODUCTION
fibrillary
to as mixed
in the identification
a recent
Of 275
Human
Grading
concordance
gliomas.
dismal
referred
of identifying
minigemistocytes
and oligodendrocytic
of the
joint
was minimal.
The association
between
tumor
and expression
of the MBP and PLP genes was
expression
tumors,
for oligodendrogliomas
methods
identification
from
1 astrocytomas.
characteristics
by histopathologically
these
multiforme
grade
stains
glial
the
glioblastoma
with
for distinguishing
Moreover,
astrocytic
tance
both
In contrast,
range
morphological
express
both
tam
with
(3).
astrocytomas
histopathological
because
marker
rate
with
for patients
Few
have
a useful
expressed
799
and
survival
patients
4) to 3.5 years
oligodendrocytes
highly
Protein
Research
Gliomas’
drogliomas
A. Norman,
R. A. Norman,
and
Basic
Cancer
encoding
finding
a useful
from
astrocytosignificant
MBP
suggests
and
that
molecular
or both.
basic protein;
PLP, proteo-
Downloaded from clincancerres.aacrjournals.org on August 3, 2017. © 1997 American Association for Cancer
Research.
800
MBP and PU’
Expression
in Human
Gliomas
Table
Tumor
codea
Agec
Diagnosis”
F
M
31
43
LGA
LGA
2
2
Th
F
35
AA
4
59
43
70
64
47
67
31
63
49
70
59
68
50
56
55
68
75
51
69
33
33
31
26
31
30
42
60
39
43
42
6
37
43
code assigned
by an “R”.
b M, male;
F, female.
C Age
at diagnosis.
d GBM,
glioblastoma
multiforme;
LGA,
e The
grading systems used are described
AND
PATIENTS
Gradee
GBM
GBM
GBM
GBM
GBM
GBM
GBM
GBM
GBM
GBM
GBM
GBM
GBM
GBM
GBM
GBM
GBM
GBM
GBM
Oligo/Astro
Oligo/Astro
Oligo/Astro
Oligo/Astro
Oligo
Oligo
Oligo
Oligo
Oligo
Rec. Oligo
Oligo
Oligo
Oligo
Oligo
to the tumor.
Recurrent
L, left; R, right;
METHODS
Specimens
and Histopathology.
Tissue samples
obtained
from patients
undergoing
resection
of malignant
All
oligodendroglioma,
patients
with
or mixed
a diagnosis
of
received
from
oligo-astrocytoma
neurosurgery,
the
were
frozen
and
RTO,
processed
for
tumor.
system
were
differentiation
consid-
evalu-
and grade and then
facing/opposing
paraffin-embedding,
was
gliomas.
the percentage
of normal
brain
tissue
admixed
Ringertz-Burger
366
D
right
was
used
(3,
15).
For
(12)
a tumor
geometric
a similar
classification
D
A
A
A
A
A
D
A
A
A
A
A
A
A
A
code followed
frontal-temporal;
and
revised
astrocytomas,
and
to grade oligodendrogliomas
or ordinary
(large)
only minigemistocytes
This
D
NA
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
D
RFT,
with
branching
area
WHO
(13)
astrocytoma
oligoastrocytoma,
we
microscopic
features:
round
field of
nuclei,
X 100
vasculature,
For
of cells
minigemis-
a tumor
primarily
to be called
mixed
resembling
gemistocytes
was
were considered
follows
RFP,
the Kernohan
and oligoas-
primarily
as mixed
protoplasmic
astrocytes.
of typical
oligodendroglioma
oligoastrocytoma,
316
NA
408
1 18
80
470
23
1460
37
485
84
362
262
237
158
281
44
233
used to grade
halos,
and
D
A
oligodendroglioma.
to be classified
perinuclear
tocytes,
consisting
astrocytes
mom with
for
Oligo,
required
the presence
of at least one
cells with typical
oligodendroglioma
insuring
as close as possible
similarity
between
the paraffin
and
frozen material.
Tissue immediately
adjacent
to the frozen tissue
graded
The
were
Status”
377
2071
912
1076
681
1428
498
942
5
1198
3239
170
561
1186
1234
the same 2-letter
is given
right temporal-occipital;
trocytOmas
neuropathologist
ated the specimens
for histopathological
type
divided
the specimens
such that corresponding
sections
oligoastrocytoma;
systems
(14)
(days)
1460
1470
L occ
B front
L temp
L front
R
RFT
R front
LTH
R pariet
L temp
L front
RTP
R pariet
Lfront
R pariet
R temp
RTO
Lfront
P0
L temp
L temp
front
R front
R front
R front
L front
R temp
Ltemp
LiP
R temp
Rocc
NA
F pariet
from the same patient
astrocytoma,
ered as sources
for tissue specimens;
selection
was based
only
on obtaining
a range of tumor
pathologies.
When
the samples
were
B, bilateral;
Survival
Lfront
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
3
2
2
2
2
3
2
3
2
2
2
2
2
2
tumor
with
Tissue
tumors.
Site
R front
L temp
low-grade astrocytoma;
Oligo/Astro,
in “Patients and Methods.”
1front, frontal; pariet, parietal; temp. temporal;
frontal-parietal;
LTH, left thalamus.
8 Survival
is in days postsurgery.
‘I A, alive;
D, deceased.
I This
tumor was analyzed in two regions.
J NA,
not available.
brain
data
Sex”
F
M
M
F
F
M
F
F
F
F
M
F
F
M
F
M
F
F
M
M
M
P0 ,
M
QK’
F
KF
F
LI
M
PK
F
QM
F
RD
M
SD
M
ST
M
SU
F
SV
M
SW
F
a Tumor code is a random
2-letter
were
Patient
LHR
01
IM
KE
KS
KV
Ia
LB
LH
LT
ME
MI
NO’
NN
NS
OF
OH
OJ
OK
RA
TK
LC
PM
right
1
the criteria
fibrillary
required.
Tuoligodendro-
developed
Downloaded from clincancerres.aacrjournals.org on August 3, 2017. © 1997 American Association for Cancer
Research.
in our
Clinical
-
A
nucleotide
DM20
splice
I
variant
.
Cancer
Research
.
E
c’
QLL
0>1
oC
c-aa
I4I5II7)_
I
I
I
I
MBP
I
,
PLP
Histone
J;
2 Reverse
transcription-PCR
sion in human malignant
glioma
for RNA quantity and integrity.
analysis of MBP and PLP exprestissue. Histone was used as a control
Fig.
422-441
T
*___
B
!.
nucleotide
I1
I
splice
variant
I
t1
I
I4i5i6I7F-
3
the
I4I617I-
3
Primer
1
location
for the genes
encoding
to
allow
A 5-mm
for
full
extension
80#{176}C
incubation
through
a 2%
agarose
fluorescence.
A
quantitation
PLP (A) and MBP
(B).
was
photographic
gel
and
Polaroid
performed
negative
expression
age,
study
(6). Clinical
gender,
surgical
data
collected
procedures,
on the patients
radiation
included
treatment,
(control)
patients
undergoing
intracerebral
gray
and
liquid
Biotecx
brain
nitrogen
All
RNA
were
chemo-
were
(16,
taken
85#{176}C
for subsequent
Reverse
lowed
by PCR
and PLP
genes
PCR
reaction
(16).
Primers
one
intron
mg of frozen
immediately
used
Reverse
to determine
in a semiquantitative
were
have
been
described
designed
and
(Fig.
run
amplified
controls
transcription
details
in a previous
for exons
fol-
of the MBP
The
8 and
of the
in a Perkin-Elmer
Histone
previously
GeneAmp
9600
MBP,
thermal
cycler
using
and 26 to 28 cycles
3 1 cycles
for histone.
sisted
of95#{176}Cfor I mm and
15 s, followed
1 mm
at 72#{176}C.
A 6-mm
72#{176}C
incubation
Inc.,
(Invitrogen
burg,
Sequencing
MD)
was
a gift
used
from
for the MBP
Dr.
Alan
PCR
were
subcloned
Diego,
CA)
fragments
into
prior
PCR-amplified
analysis
using
Technologies,
DNA
fragthe dsDNA
Inc.,
Gaithers-
State
Primer
was used
forward
Ml3/pUC
reactions.
(Ohio
the
to Se-
by the manufacturer.
sequencing
Yates
tempera-
chromatography
NH).
San
(Life
of gene
NC).
a low-melting
column
Keene,
specified
signifi-
scores
The PCR fragwere isolated
for
primers
System
Differences
statistical
Cary,
JO4 (Fig. I ; 5’-GGCGACTACAAGACCACCAT-3’)
for the PLP sequencing
reactions,
and the
was
PLP.
DNA.
primers
Elutip
Corp.,
and conditions
Our
PCR
amplification
ers generated
to span
at
an internal
3.3 was used
(16, 18). PCR
PCR
System
by 30 s at 55#{176}C,
and
used
Schuell,
RNA
Results
or no
Primer
JO4
University).
RESULTS
for PLP, 33 cycles
for
Cycle
conditions
conwas
Cycle
without
publication
3 (5’-GAAAACCCCG-
17) to provide
by
and
of the
System,
through
followed
MBP-specific
vector
primer
6 (5’-TGCCTCCGTAGCCAAATC-3’)
1; Refs.
and
using
for
Analysis
by electrophoresis
gel
and
tested
of Amplified
PLP-specific
gel,
each experiment.
trace expression,
test on the Wilcoxon
(Statistical
bromide
the
analysis
MBP
were
quencing.
The identities
of these
ments
were confirmed
by sequence
tumor
tissue.
was stored
at
expression
manner.
control
for genomic
DNA contamination.
as a RNA loading
control
as described
reactions
(Schleicher
in
RNAzol
B (Cinna/
was used to isolate
for MBP
and for exons
2 (5’-CCAAAAACTACCAAGACTATG-3
‘) and
4 (5’-CAAACACCAGGAGCCACACAA-3’)
for PLP. These primer pairs were specifically
selected
least
of
analysis.
was
TAGTCCAC-3’)
stored
encoding
Analysis
using
agarose
pCRII
Transcription-PCR.
were
and
level
sequencing
ture
genes
of
densitometric
19). Negative
classifications
Sequence
ments
amplified
isolation.
80-200
not used
DNA
at the beginning
by ethidium
was
by
by the Kruskal-Wallis
expression
from
of a mixture
frozen
tumor
cance
or spontaneous
consisted
tissues
Isolation
of Total
Cellular
RNA.
Laboratories,
Inc., Houston,
TX)
from
was
obtained
for trauma
and typically
matter.
until
specimens
resection
hemorrhage
white
total cellular
RNA
Isolated
RNA
that
-
tissue
brain
of the
among
therapeutic
treatment,
and survival
from time of first operation
(Table
1). Patient
confidentiality
was maintained
by assigning
random
two-letter
codes
to each specimen
for identification.
Normal
amplified
used
visualized
picture
and normal
brain were included
with
were ranked
as normal,
half-normal,
recent
of
was
of the reaction
to provide
a “hot start” for reducing
nonspecific
annealing.
Reaction
products
were analyzed
by electrophoresis
I I
Fig.
reaction
fragments.
at the end
of
The
was
l09-bp
l42-bp
verified
fragments
product
was
MBP-specific
(Figs.
identified
encoding
< 0.0007
by sequencing
primI and
2).
size (8) and
product.
The
as corresponding
(Fig. 1 ; Refs. 9 and 20). The PLP-specific
a 348-bp
fragment
from the normal
transcript
and a 243-bp
fragment
icant differences
among
x2; p
using
109 bp in size
fragment
corresponds
to the expected
as MBP by sequencing
the PCR
to a splice
variant
primers
amplified
of the genes
reactions
142 and
from the DM-20
splice variant.
Signiftumor classifications
in the expression
MBP
and 0.0005,
and
PLP
were
found
(approximate
respectively).
Downloaded from clincancerres.aacrjournals.org on August 3, 2017. © 1997 American Association for Cancer
Research.
801
802
MBP and PU’
Expression
in Human
Gliomas
Table 2
Tumor
code’
Diagnosis”
LHR
01-A
01-B
Th
IM
KE
KS
KV
KZ
LB
LH
LT
ME
MI
NGAh
NO-B”
NN
NS
OF
OH
OJ
OK
RA
TK
LC
PM
PG
QK
QK2h
LI
PK
QM
RD
SD
ST
SU
SV
SW
a Tumor
by an “R”.
b LGA
Grader
LGA
LGA
LGA
AA
GBM
GBM
GBM
GBM
GBM
GBM
GBM
GBM
GBM
GBM
GBM
OBM
GBM
GBM
GBM
GBM
OBM
GBM
GBM
GBM
Oligo/Astro
Oligo/Astro
Oligo/Astro
Oligo/Astro
Oligo/Astro
Oligo
Oligo
Oligo
Oligo
Oligo
Rec.Oligo
Oligo
Oligo
Oligo
Oligo
is a random
KY
code
= low-grade
Expression
of the MBP and PU’
% nonneoplastic
2
2
2
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
3
2
2
2
2
2
3
2
3
2
2
2
2
2
2
code assigned
2-letter
astrocytoma;
cellsd
genes
Sival
PLP,
The oligodendrogliomas
although
there
were
these
genes
were
expressed.
was
not
typically
analyzed
mal
solely
(Table
in only
samples,
due
D
118
80
470
23
1460
37
485
84
362
362
262
237
158
281
D
D
D
D
D
D
D
D
D
D
D
D
D
D
+/-
+
+1+1+/+/+/-
+1+/+/-
+1+1+/-
44
+/-
233
+/-
366
+1+
++
++
+/-
+
+/+/+/+/-
+
+/+/-
+1++
to the tumor.
Recurrent
astrocytoma;
GBM
glioblastoma
and
Twenty-four
25%
barely
10 oligo
detectable
tumors
approximately
+
was
2). In contrast,
5 of
brain;
normal
normal
or less
PLP
samples,
brain
because
of the tissue
gene
normal
or
half-normal
in the
3). This expression
expression
half-normal
normal
specimens
was
in 4 of
northe
in 1 sample.
of astrocytic
origin
analyzed
for
-
+
+ +
-
-
+
++
++
-
-
-
-
-
-
-
-
+
-
+
-
-
-
+
+/-
-
-
-
-
-
+/-
-
+/-
D
-
-
D
+ +
+ +
+/-
-
A
A
A
A
A
A
A
D
A
A
A
A
A
A
A
A
patient
-
+
+
+
+
+
+1-
++
-
-
++
++
++
+
++
+
+
+/-
++
++
+
+
++
++
++
+
++
++
++
is given
tissue
from
-
++
++
the same 2-letter
Oligo/Astro
half of normal;
The
majority
of the
genes encoding
samples),
and
immediately
adjacent
both
genes.
sion
in these
by
normal
samples
sion
had
little
used
no
-
and PLP. Expression
12% of the samples.
or no expression
of the
either MBP (12 of 24 samples)
or PIP (20 of 24
only two samples
had near-normal
expression
of
As in the oligodendrogliomas,
samples
cells.
from
Oligo
to the tissue
less than half of normal;
+/-
samples
code followed
= oligoastrocytoma;
the expression
of the genes encoding
MBP
of MBP or PLP was near-normal
in only
of the gene
the observed
is not attributable
The
the mixed
oligodendrogliomas
were
+
+
+/-
multiforme;
were made
PLP expression
++
D
6
1533
862
686
681
681
1428
498
511
5
1198
3239
170
561
1186
1234
tumor from the same
+/-
Expression
to admixed
represented
MBP expression8
408
NA’
of MBP
StatuI
++
+ +
+/-
both MBP and
in the amount
and at least
2; Figs. 2 and
(daysY
+/-
++
analyzed
expressed
distinct
differences
almost
so in 8 of 10 specimens
remaining
two samples
(Table
cells
in
gliomas
D
A
A
D
NA
oligodendroglioma;
rec = recurrent.
C The
grading systems used are described
in the Materials
and Methods.
d
=
25-50%;
+
approximately
25%; +/= minimal.
Determinations
for RT-PCR analysis.
e Survival
is in days post-surgery.
1A = alive; D = deceased.
S
= expression
equal to that observed
detectable
expression.
h This
tumor was analyzed
in two regions.
‘ NA,
not available.
and mixed
1460
1470
858
316
NA
++
AA = anaplastic
in gliomas
expression
of MBP
oligoastrocytomas
and astrocytomas.
encoding
solely
MBP
was
Not
expres-
to contamination
and
PIP
in tissue
had elements
of both
surprisingly,
expres-
somewhat
random
Downloaded from clincancerres.aacrjournals.org on August 3, 2017. © 1997 American Association for Cancer
Research.
in that
Clinical
A
.
Additionally,
cells
that
lation
12
a.
E
(22).
PLP
have
specimens
from
statistically
significant
tumor
I-
0
z
normal
15
The
12
that
in each
E
in these
*2
PLP (A) and MBP (B) expression
in human malignant
glioma
tissue. Expression
was quantitated
by densitometric
analysis and normalized to the expression
of histone to control for RNA quantity and
integrity. Results are expressed compared
with the expression
in normal
brain tissue (Table 2).
(2 of 5) of the
showed
trast,
none
samples
showed
near-normal
expression,
and
20%
had
no expression.
In con-
of the samples
had
near-normal
expression
of PLP,
60% had approximately
half-normal
expression,
samples
had little or no PLP expression.
During
this
representing
study,
we also
different
regions
analyzed
from
two
the
differences
of normal
did
brain
the
separate
low-grade
0! and two from the mixed oligoastrocytoma
differences
in gene expression
in various
these
and
lineage
astrocytoma
not
solely
reflect
tissue
found
in the tumor
differences
their
ability
to produce
encoding
MBP
cal identification
drogliomas,
ing results.
tumors
for
mature
through
in
poor
(7, 2 1). Some
oligodendrogliomas,
is
of genes
at immunohistochemiin gliomas,
oligodenhave yielded
myelin
proteins
authors
whereas
have
found
others
Whether
There
is evidence,
however,
in vitro in cell lines obtained
that
from
nuclei
exami-
of MBP
gene
regulation
and
found
underscores
the need
for
in addition
to analysis
of
to a higher
absence
of MBP
with other
In all cases,
grade
and PLP
the patterns
a higher
indicate
tumors
than
of tumor
gene
astroas the
in which
astrocytes.
Interest-
of tumor
QK
astrocytic
compo-
alterations
found
also
and PLP gene
MBP or PLP.
is unclear.
expression
that
cell such
tumors
grade
genetic
The
Ex-
may
stem
regions
undergoing
greater
of PLP.
in their levels of MBP
did not express
either
contained
cells
correlates
sample.
tumors
in neighboring
different
with
that
be oligodendrocytic
from
intermediate
controversial.
a pluripotent
is induced
region
than
remains
by these
may
an
typically
MBP
tumors
from
differences
Region
QK-2
this
genes,
to the oligodendroglial
arise
samples
or contained
Our
MBP
leading
to
However,
the
in region
QK-2
studies
we have done
using
this same
gene expression
in region
QK-2
has fol-
set by more
absence
lihood
conflictin these
demonstrate
subtype
and
PLP.
malignant
expression
a statistically
and
High
the expression
expression
for a diagnosis
of expression
of an astrocytic
examined,
gliomas,
data
tumor
evidence
be useful
astrocytic
tumors
( I 6,
significant
association
of the genes
of both
of oligodendroglioma,
of either of these
tumor.
Although
of the genes
MBP
encoding
MBP
PLP
and the
genes suggests
more samples
as an adjunct
to histologically
based
particularly
when the histopathological
encodand
a likemust be
and PLP
may
diagnoses
of
features
alone
are inconclusive.
staining
have
only
found MBP staining
in normal
white matter (7). This work may
have been hampered
by difficulties
in obtaining
reliable
immunohistochemical
staining
because
of the paucity
of good antibodies.
pressed
of the specimen
displayed
transcripts
change
two
between
oligodendrocytes
genes
It is un-
of normal
expression
and
encoding
mixed
or they
in the
sample.
the expression
Prior attempts
gene products
and mixed oligoastrocytomas
Tissue
staining
for the
has been
MBP
myelin
and PLP.
of these
of
as
25).
DISCUSSION
characteristic
gene
(24),
cell
provides
salient
tumors
of the myelin
02A
ing
The
the
the chaotic
oligoastrocytomas
may
lowed
QK. In both cases,
regions
were noted,
of these
by histopathological
examination
is closer
progression
samples
is intriguing.
with
reflect
malignant
They
nent
other
correlate
cytomas.
demonstrated
expression.
half-normal,
or both
determined
may
of myelin
ingly,
40%
not
of these
malignant
40%
was
of the
pression
their
of one
contamination
mixed
histogenesis
3
oligo-
as much
tumors
the proportion
of expression
expression
15
large
whereas
often
a
and
express
or PLP,
genes,
was
markers.
The
I
expression
these
expression
histopathological
degree
IS-
There
gene
because
result
molecular
iranin tissue
tumors.
reflected
highly
careful
0
reverse
genes
brain
tissue
did
This
used
to MBP
between
finding
brain
and
PLP.
we
MBP
to express
trans-
antibodies
of these
803
in cultured
without
did not typically
encoding
multiforme
specimen
nation
156
U)
done
Research
tissue.
this
by normal
10
tumors
genes
glioblastoma
likely
B
to obtain,
malignant
near-normal
in two
reliable
correlation
tend
brain
work
be present
the expression
Astrocytic
of the
dendrogliomas
!
0
z
difficult
human
subtype.
from
may
Because
to analyze
amounts
i#{224}Ilgo”
.
amount
been
II..
z
and
(23).
to
0
is evidence
transcription
scription-PCR
0
Fig.
gene
of the message
and
15
there
PLP
Cancer
these
genes
are
oligodendrogliomas
ex-
ACKNOWLEDGMENTS
We acknowledge
the excellent
technical
assistance
of Susan N.
Rhodes and the editorial assistance
of Dr. Shelley A. Kick. We thank
Drs. Peter C. Johnson,
Joan Rankin Shapiro, and William R. Shapiro,
and Linda
Gower-Malatesta,
for helpful
discussions
and patient
follow-up
data.
Downloaded from clincancerres.aacrjournals.org on August 3, 2017. © 1997 American Association for Cancer
Research.
804
MBP and PLP Expression
in Human
Gliomas
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Expression of the genes encoding myelin basic protein and
proteolipid protein in human malignant gliomas.
J G Golfinos, S A Norman, S W Coons, et al.
Clin Cancer Res 1997;3:799-804.
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