ArticleNeuro-oncology advances
Delta-like ligand 3 expression in isocitrate dehydrogenase-mutant and isocitrate dehydrogenase-wildtype glioma is largely retained at recurrence, supporting its potential as a therapeutic target.
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Abstract
Background: Delta-like ligand 3 (DLL3), an inhibitory Notch ligand, is now explored as a therapeutic target in recurrent diffuse glioma. Since clinical trials may select patients with recurrent glioma based on DLL3 expression in the primary tumor, this study aims to determine whether initial DLL3 expression in glioma is retained at recurrence. Methods: 198 formalin fixed, paraffin-embedded (FFPE) samples of paired primary and recurrent gliomas were retrieved from the biobank in the Erasmus MC, Rotterdam, the Netherlands. The cohort included oligodendroglioma, isocitrate dehydrogenase mutant (IDHmt) and 1p/19q co-deleted ( Results: DLL3 expression was detected in the majority of glioma samples (86%, 164/190). Expression levels were highest in oligodendroglioma (94% medium or high) and astrocytoma (78.4% medium or high), and lowest in glioblastoma (42% medium or high). 26/190 samples were DLL3-negative. In most patients, DLL3 expression stayed in the same category or increased at recurrence (oligodendroglioma 87.6%, astrocytoma 66.6%, glioblastoma 77.2%). Loss of initial DLL3-positivity at recurrence occurred in only 7/91 patients (7.7%). Conclusion: DLL3 expression level is retained or increased in the majority of recurrent gliomas. Inclusion in trials with DLL3-targeting agents in recurrent glioma based on primary tumor material is justified, depending on the required level of DLL3 positivity for inclusion.
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