Dataset Information

PD-L1 Immunohistochemistry Comparability and Their Correlation with Clinical Characteristics in NSCLC.

ABSTRACT: Background:PD-L1 expression is an important predictive factor of response to therapy with immune checkpoint inhibitors (ICIs). This study was designed to retrospectively analyze the concordance of PD-L1 measurements using three different assays (Dako22C3, Dako28-8, and SP142) in NSCLC patients and to find possible predictors of high PD-L1 expression. Materials and Methods:Data of 144 patients with histologically confirmed NSCLC and available PD-L1 measurements treated at the Taoyuan General Hospital from 2018 to 2019 were retrospectively reviewed in the study. Patients' characteristics, including age, sex, clinical stage (T, N, and M) of NSCLC (AJCC, 8th edition), and EGFR/ALK alterations, were analyzed for association with PD-L1 expression. Results:Measurements of PD-L1 expression levels with Dako22C3 and Dako28-8 were comparable while SP142 showed lower levels of PD-L1 expression. The overall agreement between Dako22C3 and Dako28-8 was 82.2% and 91.6% for both 1% and 50% TPS cut-offs, respectively. The above findings were confirmed by Cohen's kappa. In addition, we found that PD-L1 expression was significantly associated with advanced N stage but not with T and M stages. Conclusion:Dako22C3 and Dako28-8 showed comparable results in assessing PD-L1 levels. Future prospective studies are needed to validate these findings. N stage may be a good predictor for PD-L1 expression.

SUBMITTER: Wu CE

PROVIDER: S-EPMC7655253 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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PD-L1 Immunohistochemistry Comparability and Their Correlation with Clinical Characteristics in NSCLC.

Wu Chiao-En CE Chang Ching-Fu CF Kou-Sheng Liao L Chiang Ju J Lee Shih-Wei SW Chiu Yu-Chi YC

Analytical cellular pathology (Amsterdam) 20201102

<h4>Background</h4>PD-L1 expression is an important predictive factor of response to therapy with immune checkpoint inhibitors (ICIs). This study was designed to retrospectively analyze the concordance of PD-L1 measurements using three different assays (Dako22C3, Dako28-8, and SP142) in NSCLC patients and to find possible predictors of high PD-L1 expression.<h4>Materials and methods</h4>Data of 144 patients with histologically confirmed NSCLC and available PD-L1 measurements treated at the Taoyu ...[more]

PMID: 33204603

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Project description:BackgroundExosomes are 50-150 nm endocytic vesicles secreted by almost all type of cells that carry bioactive molecules from host. These small vesicles are considered to be novel cross-talk circuits established by tumor cells and tumor microenvironment. Previous studies have shown certain biological influence of exosomal programmed cell-death ligand 1 (Exo-PD-L1) on immune suppression and dysfunction. The aim of the current study was to investigate the impact of Exo-PD-L1 and soluble PD-L1 (sPD-L1) on non-small cell lung cancer (NSCLC) and explore the concordance between Exo-PD-L1 and PD-L1 expression in matched tumor tissues in NSCLC patients.Methods85 consecutive patients from April 2017 to December 2017 at General Hospital of Eastern Command Theatre who were primarily diagnosed with NSCLC and 27 healthy individuals were enrolled in this study. Two milliliters of whole blood samples were collected from each participant and further centrifuged. Exosomes were derived from serum using the commercial kit (Total Exosome Isolation Kit), which was further identified by Western blotting analysis (CD63/TSG101), transmission electron microscope analysis (TEM) and nanoparticle tracking analysis (NTA). Exosomes were next solubilized for Exo-PD-L1 detection by enzyme-linked immuno-sorbent assay (ELISA). PD-L1 expression in matched tissue were assessed by PD-L1 immunohistochemistry (IHC) (clone 28-8) assay. Tumor proportion score (TPS) ≥ 1% was deemed as "positive" in this study and TPS < 1% was deemed as "negative". Written informed consent were obtained before acquisition of all data and biological sample. Data were analyzed using SPSS 20.0 and Graphpad Prism 5 software. Chi square test was conducted to estimate the correlation between Exo-PD-L1 levels, sPD-L1 levels, PD-L1 IHC profiles and clinicopathological features. For all analysis, a two-sided p < 0.05 was considered significant statistically.ResultsExo-PD-L1 levels were higher in NSCLC patients with advanced tumor stage, larger tumor size (> 2.5 cm) (p < 0.001), positive lymph node status (p < 0.05) and distant metastasis (p < 0.05). In contrast, sPD-L1 levels were not different between NSCLC patients and healthy donors, it was not correlated with any clinicopathologic features except for tumor size (> 2.5 cm) (p < 0.05). In addition, Exo-PD-L1 levels showed slight correlation with sPD-L1 levels (Spearman's correlation at r = 0.3, p = 0.0027) while no correlation with PD-L1 IHC profiles was detected.ConclusionsIn conclusion, Exo-PD-L1, but not sPD-L1, was correlated with NSCLC disease progression, including tumor size, lymph node status, metastasis and TNM stage. However, Exo-PD-L1 was not associated with PD-L1 IHC status.

Project description:BackgroundFor non-small cell lung cancer (NSCLC), treatment with pembrolizumab is limited to patients with tumours expressing PD-L1 assessed by immunohistochemistry (IHC) using the PD-L1 IHC 22C3 pharmDx (Dako, Inc.) companion diagnostic test, on the Dako Autostainer Link 48 (ASL48) platform. Optimised protocols are urgently needed for use of the 22C3 antibody concentrate to test PD-L1 expression on more widely available IHC autostainers.MethodsWe evaluated PD-L1 expression using the 22C3 antibody concentrate in the three main commercially available autostainers Dako ASL48, BenchMark ULTRA (Ventana Medical Systems, Inc.), and Bond-III (Leica Biosystems) and compared the staining results with the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform. Several technical conditions for laboratory-developed tests (LDTs) were evaluated in tonsil specimens and a training set of three NSCLC samples. Optimised protocols were then validated in 120 NSCLC specimens.ResultsOptimised protocols were obtained on both the VENTANA BenchMark ULTRA and Dako ASL48 platforms. Significant expression of PD-L1 was obtained on tissue controls with the Leica Bond-III autostainer when high concentrations of the 22C3 antibody were used. It therefore was not tested on the 120 NSCLC specimens. An almost 100% concordance rate for dichotomized tumour proportion score (TPS) results was observed between TPS ratings using the 22C3 antibody concentrate on the Dako ASL48 and VENTANA BenchMark ULTRA platforms relative to the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform. Interpathologist agreement was high on both LDTs and the PD-L1 IHC 22C3 pharmDx kit on the Dako ASL48 platform.ConclusionAvailability of standardized protocols for determining PD-L1 expression using the 22C3 antibody concentrate on the widely available Dako ASL48 and VENTANA BenchMark ULTRA IHC platforms will expand the number of laboratories able to determine eligibility of patients with NSCLC for treatment with pembrolizumab in a reliable and concordant manner.

Dataset Information

PD-L1 Immunohistochemistry Comparability and Their Correlation with Clinical Characteristics in NSCLC.

Publications

PD-L1 Immunohistochemistry Comparability and Their Correlation with Clinical Characteristics in NSCLC.

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