Title:
Activated leukocyte cell adhesion molecule is expressed in neuroepithelial neoplasms and decreases with tumor malignancy, matrix metalloproteinase 2 expression, and absence of IDH1R132H mutation.

Abstract:
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.