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Immunohistochemical
study for O6-methylguanine-DNA methyltransferase in the
non-neoplastic and neoplastic components of gliomas
Satoshi Nakasu*, Tadateru
Fukami, Kazumi Baba, Masayuki Matsuda
Department of Neurosurgery,
Shiga University of Medical Science, Seta, Ohtsu,Shiga-ken, 520-2192,
Japan. *Corresponding Author (snakasu@belle.shiga-med.ac.jp).
Although the expression O6-methylguanine-DNA
methyltransferase (MGMT) is an important hallmark for decision of
nitrosourea chemotherapy for glioma patients, no immunohistochemical
method for analysis of MGMT has been standardized yet.
Gliomas usually contain non-neoplastic cells even deep in the
tumor.
It is not known which of these components expresses MGMT.
To clarify this point, we investigated MGMT expression in the
non-neoplastic cells in autopsy and surgical specimens by
immuno-histochemistry.
High grade gliomas were also studied to find a cut-off point for
treatment decision.
MGMT immunohistochemistry in the normal brain or brain with
non-neoplastic disease revealed nuclear staining in some endothelial
cells, inflammatory cells, ependymal cells, astrocytes and
oligodendroglias.
Some cells were double stained with CD68 (macrophages or
microglias).
The neurons were consistently MGMT-negative.
High grade gliomas always contained an MGMT-positive non-neoplastic
component.
Although the endothelial cells were easily distinguished from the
neoplastic cells, other cells were often mistaken for tumor
cells.
The population of MGMT-positive non-neoplastic cells was usually less
than 10%.
We set a cut off-point at 10% between the positive and negative groups
because the statistical difference in the overall survival was most
distinct at this value.
In 51 high grade glioma patients, who received both radiotherapy and
chemotherapy with nimustine (ACNU), the median overall survival of the
MGMT-negative group (23months) was significantly longer than that of
the MGMT-positive group (14months) (P<0.009).
Multivariate analysis revealed that the negative MGMT expression was a
significant prognostic variable next to the degree of surgical removal
for the overall survival.
In the MGMT-positive group, addition of platinum-based chemotherapy
did not improve the survival.
Keywords: CD68, glioblastoma,
immunohistochemistry, malignant glioma, O6-methylguanine-DNA
methyltransferase
Copyright © 2004 Kluwer Academic Publishers.
All rights reserved
Source: http://ipsapp009.kluweronline.com/IPS/content/ext/x/J/5042/I/126/A/9/abstract.htm
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