Programmed Death-Ligand 1 Expression across Multiple Assays in Ovarian Cancer: A Comparative Analysis.

Area of Science:

• Oncology
• Immunology
• Pathology

Background:

• Ovarian cancer is challenging to treat, with limited response to immune checkpoint inhibitors (ICIs).
• Standardization of programmed cell death-ligand 1 (PD-L1) assays and cut-off values is lacking, complicating clinical decisions.
• PD-L1 expression is a key biomarker for ICI efficacy.

Purpose of the Study:

• To evaluate the concordance among commonly used PD-L1 immunohistochemistry assays in ovarian cancer.
• To assess changes in PD-L1 expression following chemotherapy.
• To inform standardized testing protocols for PD-L1 in ovarian cancer.

Main Methods:

• Analysis of 29 ovarian cancer tissue samples using five validated PD-L1 assays (Dako 22C3, Ventana SP263, Ventana SP142, Dako 28-8, Ventana 22C3).
• PD-L1 positivity assessed using combined positive score (CPS), immune cell (IC), or tumor proportion score (TPS) at 1%, 5%, and 10% cut-offs.
• Concordance analysis (OPA, Cohen's kappa) and pre- vs. post-chemotherapy PD-L1 expression evaluation.

Main Results:

• PD-L1 positivity rates varied from 15.8% (SP142) to 29.8% (Dako 22C3, SP263) at 1% CPS cut-off.
• SP142 assay showed the lowest concordance; Dako 22C3 demonstrated high agreement with SP263, 28-8, and Ventana 22C3.
• Chemotherapy increased PD-L1 positivity, with 28% of patients converting from negative to positive.

Conclusions:

• Ovarian cancer PD-L1 expression is assay-dependent, highlighting the need for standardized testing.
• Increased PD-L1 expression post-chemotherapy is crucial for guiding ICI therapy timing.
• Further research is needed to validate findings and refine clinical applications of PD-L1 testing.