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

Luning R, Maas SL, French PJ, Hoogstrate Y, van Hijfte L, Head R, de Heer I, van den Bosch TP, Woehrer A, van den Bent MJ, Geurts M (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Neuro-Oncology Advances Oxford University Press

Book Volume: 8

Journal Issue: 1

DOI: 10.1093/noajnl/vdag027

Abstract

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 (n = 36), astrocytoma IDHmt (n = 38) and glioblastoma IDH wildtype (IDHwt) (n = 124). DLL3 protein expression was assessed by immunohistochemistry, and samples were categorized as DLL3-negative (0%), DLL3-low (>0-10%), DLL3-medium (10%-50%) and DLL3-high (>50%) based on the estimated percentage of DLL3-positive cells within vital tumor tissue. 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.

Authors with CRIS profile

Levi van Hijfte Department of Neurosurgery

Involved external institutions

Erasmus University Medical Center (MC) NL Netherlands (NL) Medizinische Universität Innsbruck AT Austria (AT)

How to cite

APA:

Luning, R., Maas, S.L., French, P.J., Hoogstrate, Y., van Hijfte, L., Head, R.,... Geurts, M. (2026). 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. Neuro-Oncology Advances, 8(1). https://doi.org/10.1093/noajnl/vdag027

MLA:

Luning, Rosa, et al. "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." Neuro-Oncology Advances 8.1 (2026).

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