Intrapatient Tumor Heterogeneity in IHC Interpretation Using PD-L1 IHC 22C3 pharmDx.

Area of Science:

• Oncology
• Pathology
• Immunohistochemistry

Background:

• Tumor heterogeneity can complicate immunohistochemical (IHC) interpretation, potentially influencing cancer patient management decisions.
• Programmed cell death ligand-1 (PD-L1) IHC 22C3 pharmDx is a companion diagnostic aiding in patient selection for pembrolizumab therapy.

Purpose of the Study:

• To investigate the impact of tumor heterogeneity on PD-L1 expression evaluation using PD-L1 IHC 22C3 pharmDx.
• To assess the reproducibility of PD-L1 IHC 22C3 pharmDx staining across different tumor sample assessments.

Main Methods:

• Evaluated PD-L1 diagnostic status using PD-L1 IHC 22C3 pharmDx in various cancer types (NSCLC, gastric, urothelial, HNSCC, esophageal, TNBC).
• Assessed agreement within specimen blocks (Intra-Block), between blocks from the same resection (Intra-Case), and between primary and metastatic specimens.
• Analyzed consistency of PD-L1 expression across different tissue sections and patient samples.

Main Results:

• Intrablock and intracase agreement for PD-L1 diagnostic status exceeded 75%.
• Primary versus metastatic specimen agreement was above 50%.
• PD-L1 expression remained consistent across sections (≥150 µm), blocks, and primary/metastatic sites, irrespective of microenvironment changes.

Conclusions:

• PD-L1 IHC 22C3 pharmDx demonstrates reproducible PD-L1 expression assessment, even with tumor heterogeneity.
• These findings support the reliability of PD-L1 IHC 22C3 pharmDx for determining patient eligibility for pembrolizumab treatment.
• Histopathologists and oncologists can be confident in the consistency of PD-L1 evaluation across different samplings of a single tumor specimen.