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High-accuracy Detection of PD-L1 3'-UTR Disruption by Immunohistochemistry and Fluorescence in Situ Hybridization on Formalin-fixed Paraffin-embedded Sections

  • 0Pathology Project for Molecular Targets, Cancer Institute.
The American Journal of Surgical Pathology +

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March 3, 2025

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March 3, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Structural variations in the PD-L1 gene 3'-UTR are linked to overexpression. Immunohistochemistry and FISH effectively detect these PD-L1 gene abnormalities in lymphoma, offering an alternative to sequencing.

Area Of Science

  • Oncology
  • Molecular Biology
  • Genetics

Background

  • Programmed death-ligand 1 (PD-L1) structural variations (SVs) in the 3'-untranslated region are associated with PD-L1 overexpression.
  • Detecting PD-L1 SVs is crucial for understanding lymphoma pathogenesis and treatment response.

Purpose Of The Study

  • To evaluate the applicability of immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for detecting PD-L1 SVs in lymphoma.
  • To compare IHC and FISH methods with target-capture sequencing for PD-L1 abnormality assessment.

Main Methods

  • Screened 1052 lymphoma samples using IHC.
  • Evaluated 99 IHC-positive samples with FISH (58 non-Hodgkin lymphoma [NHL], 41 Hodgkin lymphoma [HL]).
  • Performed target-capture sequencing on 73 samples.

Main Results

  • Abnormal FISH findings were detected in all evaluated samples.
  • PD-L1 SVs were identified in 39% of NHL and 3% of HL samples via sequencing.
  • The combined IHC/FISH approach showed high positive (94%) and negative (96%) predictive values for detecting PD-L1 SVs.

Conclusions

  • IHC and FISH are effective methods for detecting PD-L1 gene abnormalities in lymphoma.
  • This approach serves as a viable alternative to target-capture sequencing for evaluating PD-L1 SVs.

Keywords: