Integrin inhibitors targeting αv series
integrins are being tested for their therapeutic potential in patients with
brain tumors, but pathologic studies have been limited by lack of
antibodies suitable for immunohistochemistry (IHC) on
formalin-fixed,
paraffin-embedded specimens. We compared the expression of αv
integrins by IHC in
brain tumor and normal human brain samples with gene expression data in a public database using new rabbit
monoclonal antibodies against αvβ3, αvβ5, αvβ6, and αvβ8 complexes using both manual and automated microscopy analyses. Glial
tumors usually shared an αvβ3-positive/αvβ5-positive/αvβ8-positive/αvβ6-negative phenotype. In 94 WHO (World Health Organization)
grade II astrocytomas, 85
anaplastic astrocytomas WHO grade III, and 324
glioblastomas from archival sources, expression of
integrins generally increased with grade of
malignancy.
Integrins αvβ3 and αvβ5 were expressed in many
glioma vessels; the intensity of vascular expression of αvβ3 increased with grade of
malignancy, whereas αvβ8 was absent. Analysis of gene expression in an independent cohort showed a similar increase in
integrin expression with
tumor grade, particularly of ITGB3 and ITGB8; ITGB6 was not expressed, consistent with the IHC data. Parenchymal αvβ3 expression and ITGB3 gene overexpression in
glioblastomas were associated with a poor prognosis, as revealed by survival analysis (Kaplan-Meier logrank, p = 0.016). Together, these data strengthen the rationale for anti-
integrin treatment of glial
tumors.