Related Experiment Video
Updated: Feb 4, 2026

Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
The use of cytological material in melanoma for programmed death ligand 1 immunostaining
Eva Bashover1, Aileen Grace Arriola1, Cicily T Joseph1
1Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Objective:
Interest in immune therapies has exploded since the 2014 approval of first-generation programmed cell death 1 blocking antibodies for use in advanced melanoma. Clinical trials have focused primarily on histological material as the gold standard for evaluating programmed death ligand 1 (PD-L1) by immunoperoxidase (IPOX) studies. Studies validating the use of cytological specimens in the assessment of PD-L1 by IPOX staining are needed to optimise tissue utilisation in complementary diagnostic testing.
Methods:
Twenty-three melanoma surgical biopsies (SBx) with an IPOX stain for PD-L1 clone 28-8, and a corresponding cytological specimen from the same patient, adequate for PD-L1 evaluation, were selected. Cell-transfer cell blocks (CBs) and conventional CBs were used to perform PD-L1 testing. Tumour proportion scores (TPS) were generated and the results were correlated with the corresponding SBx.
Results:
Overall agreement (OA) using a ≥1% TPS cut-off for SBx compared to CB was 88.9%, positive percent agreement (PPA) was 87.5%, and negative percent agreement (NPA) was 100%, OA using a ≥5% TPS cut-off was 55.6%, PPA was 42.9%, and NPA was 100%. SBx compared to cell-transfer CB using a ≥1% TPS cut-off had an OA of 65.2%, a PPA of 55.6%, and a NPA of 100%, while a ≥5% TPS cut-off generated an OA of 52.2%, a PPA of 35.7%, and a NPA of 77.8%.
Conclusion:
Our results demonstrate that cytological material, particularly conventional CB, is a viable alternative for evaluating PD-L1 in melanoma cases and suggest that a lower threshold (≥1%) may be beneficial when evaluating cytological material.
Insights
Cytological specimens, especially conventional cell blocks, are effective for assessing programmed death-ligand 1 (PD-L1) in melanoma. A lower PD-L1 threshold (≥1%) may improve accuracy in cytological evaluations.
Area of Science:
- Oncology
- Immunology
- Pathology
Background:
- Immune therapies for advanced melanoma have surged since 2014.
- Histological material is the standard for evaluating programmed death-ligand 1 (PD-L1) via immunoperoxidase (IPOX) studies.
- Optimizing tissue utilization for PD-L1 testing requires validation of cytological specimens.
Purpose of the Study:
- To assess the utility of cytological specimens for PD-L1 evaluation in melanoma.
- To compare PD-L1 assessment in cytological samples with corresponding surgical biopsies.
- To determine optimal cut-offs for PD-L1 evaluation in cytological material.
Main Methods:
- Twenty-three melanoma surgical biopsies (SBx) and corresponding cytological specimens were analyzed.
- PD-L1 expression was assessed using immunoperoxidase (IPOX) staining with clone 28-8.
- Tumor proportion scores (TPS) were generated and compared between SBx and cell-transfer cell blocks (CBs) and conventional CBs.
Main Results:
- Conventional cell blocks showed high overall agreement (88.9%) with surgical biopsies at a ≥1% TPS cut-off.
- Agreement varied with different cut-offs and cell block types, with cell-transfer CBs showing lower concordance.
- Negative percent agreement was consistently high across all comparisons.
Conclusions:
- Cytological material, particularly conventional cell blocks, serves as a viable alternative for PD-L1 assessment in melanoma.
- A lower PD-L1 threshold (≥1%) may be more suitable for cytological specimens.
- This finding supports optimizing tissue utilization in diagnostic testing.
Related Concept Videos
Ligand Binding Sites
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Ligand Binding Sites
Metal-Ligand Bonds
In these complexes, transition metals form coordinate covalent bonds, a kind of Lewis acid-base interaction in which both of the electrons in the bond are contributed by a donor (Lewis base) to an electron acceptor (Lewis acid). The Lewis acid in...
Ligand Binding and Linkage
Ligand Binding and Linkage
Members Made of Elastoplastic Material
As the bending moment...

