Comparison of four DLL3 antibodies performance in high grade neuroendocrine lung tumor samples and cell cultures

Luka Brcic1, Christian Kuchler2, Sylvia Eidenhammer2

  • 1Diagnostic and Research Center for Molecular BioMedicine, Diagnostic and Research Institute of Pathology, Medical University of Graz, Neue Stiftingtalstrasse 6, 8010, Graz, Austria. luka.brcic@medunigraz.at.

Abstract

Insights

This study evaluated DLL3 antibodies for small cell lung cancer (SCLC) diagnostics. The clinical trial antibody showed superior performance, and RB1 loss correlated with DLL3 positivity in SCLC.

Area of Science:

  • Oncology
  • Pathology
  • Immunohistochemistry

Background:

  • Small cell lung cancer (SCLC) has a poor prognosis with limited therapeutic advancements.
  • DLL3-targeted antibody-drug conjugate therapy shows promise for SCLC.
  • DLL3 immunohistochemistry is crucial for patient selection for this therapy.

Purpose of the Study:

  • To assess the efficacy of different DLL3 antibodies for SCLC diagnosis.
  • To evaluate DLL3 expression in high-grade neuroendocrine tumors.
  • To correlate DLL3 expression with Rb1 loss and TP53 mutation.

Main Methods:

  • Immunohistochemical analysis of 24 SCLC and 29 LCNEC cases using four DLL3 antibodies.
  • Validation cohort included 46 SCLC samples and SCLC cell lines.
  • Microscopic evaluation and manual scoring of DLL3, TP53, and Rb1 expression.

Main Results:

  • Significant variability in agreement among DLL3 antibodies.
  • The clinical trial antibody demonstrated superior specificity and sensitivity in cell cultures.
  • RB1 loss correlated with DLL3 positivity in SCLC (p=0.037), but not in LCNEC.

Conclusions:

  • The DLL3 antibody from the clinical trial is superior for detecting DLL3 expression.
  • Cell cultures serve as reliable positive and negative controls for DLL3 antibody validation.
  • DLL3 expression in LCNEC warrants further investigation for therapeutic strategies.

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