Diffuse growth of
gliomas is based on enhanced cell migration and remodeling of the extracellular matrix. Up-regulation of
matrix metalloproteinases in
gliomas is associated with a poor prognosis. The activated
leukocyte adhesion molecule is considered to be indispensable for conversion of
matrix metalloproteinase 2 into its active form. We therefore investigated the expression of activated
leukocyte adhesion molecule in 9 malignant glial cell lines, 105 normal/reactive human brain specimens, 248
astrocytomas/
glioblastomas, 98
ependymomas, 35
oligodendrogliomas, 10
neurocytomas, 10
primitive neuroectodermal tumors (
PNET), and 36
medulloblastomas by immunohistochemistry and in selected cases by
reverse transcriptase polymerase chain reaction. Correlation between activated
leukocyte adhesion molecule expression and
tumor grades and entities, proliferation activity,
matrix metalloproteinase 2 expression, prognostic
isocitrate dehydrogenase (IDH)1 mutation (R132H) status, O-6-methylguanine
DNA-
methyltransferase (MGMT) promoter status, or association with patient survival were analyzed. All
oligodendrogliomas were strongly activated
leukocyte adhesion molecule positive. Numbers of activated
leukocyte adhesion molecule positive
tumors were higher in
glioblastomas (93%) than in diffuse
astrocytomas (83%), but mean expression intensity was significantly reduced.
Anaplastic ependymomas (68%) exhibited reduced numbers of activated
leukocyte adhesion molecule-positive
tumors and staining intensity compared with lower-grade
ependymomas (85%). Activated
leukocyte adhesion molecule expression in
gliomas was independent of proliferative activity, MGMT status, patient survival, and age, whereas
gliomas with IDH1 (R132H) mutation had significantly higher activated
leukocyte adhesion molecule levels than their wild-type counterparts.
Matrix metalloproteinase 2-negative
glioblastomas exhibited significantly reduced activated
leukocyte adhesion molecule expression levels compared with
astrocytomas. In summary, our findings indicate that activated
leukocyte adhesion molecule expression levels in
gliomas are probably linked to other mechanisms than its supposed role as regulator of
matrix metalloproteinase 2.