Abstract
BackgroundDetection of programmed cell death ligand-1 (PD-L1) by immunohistochemistry (IHC) has been commonly used to predict the efficacy of treatment with PD-1/PD-L1 inhibitors. However, there is limited literature regarding the reliability of PD-L1 testing using malignant pleural effusion (MPE) cell blocks. Here, we assess PD-L1 expression in sections from MPE cell blocks and evaluate the value of IHC double staining in the interpretation of PD-L1 expression.MethodsIn all, 124 paired formalin-fixed tissues from advanced NSCLC patients, including MPE cell blocks and matched histology samples, were included. PD-L1 expression was assessed using the SP263 assay, and the tumor proportion score (TPS) and the staining intensity were evaluated. PD-L1 staining results were also compared between IHC double and single staining techniques.ResultsPD-L1 expression was concordant in most paired cases (86/101, 85.1%) among three TPS cut-offs (<1%, 1–49% and ≥ 50%), with a kappa value of 0.774. Moreover, a significant difference in PD-L1 expression between MPE cell blocks and biopsy samples was observed (p = 0.005). For the 15 discordant pairs, 13 MPE cell block samples showed increased expression of PD-L1. Compared with the standard IHC single PD-L1 assay, double staining with anti-TTF-1 and anti-PD-L1 revealed a negative effect on PD-L1 expression testing and resulted in weaker staining intensity and a lower TPS (p = 0.000).ConclusionsMPE cell block samples are good candidates for PD-L1 expression detection in advanced NSCLC patients. The mechanism and clinical significance of the higher PD-L1 expression rate in MPE cell blocks compared with small biopsy samples remain to be evaluated prospectively.
Highlights
Detection of programmed cell death ligand-1 (PD-L1) by immunohistochemistry (IHC) has been commonly used to predict the efficacy of treatment with PD-1/PD-L1 inhibitors
IHC double staining with PD-L1 and transcription factor-1 (TTF-1) Positive cases with inconsistent PD-L1 expression in the paired samples, as well as other difficult-to-interpreted samples, were sectioned again for IHC double staining with anti-TTF-1 and anti-PD-L1
IHC double staining with anti-TTF-1 and anti-PD-L1 Twenty-nine of the 32 samples were subjected to IHC double staining with antibodies to TTF-1 and PD-L1
Summary
Detection of programmed cell death ligand-1 (PD-L1) by immunohistochemistry (IHC) has been commonly used to predict the efficacy of treatment with PD-1/PD-L1 inhibitors. There is limited literature regarding the reliability of PD-L1 testing using malignant pleural effusion (MPE) cell blocks. Tumor PD-L1 expression is not a perfect biomarker with regard to its ability to predict the efficacy of immunotherapy, PD-L1 detection by immunohistochemistry (IHC) is currently the most convenient and economical method, and it has commonly been used to identify patients who may be more likely to benefit from immunotherapy with PD-1/PD-L1 inhibitors. Due to the heterogeneity of PD-L1 expression by tumor cells, assessing the reliability and comparability of PD-L1 testing on MPE cell blocks by a comparison study is necessary
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