Distribution and concordance of PD-L1 expression by routine 22C3 assays in East-Asian patients with non-small cell lung cancer
Abstract Background Currently, programmed death ligand-1 (PD-L1) expression has been widely applied in clinical trials and real-world clinical practice as a major biomarker for the efficacy of immune-checkpoint inhibitors. The purpose of this study is to reveal the distribution and concordance of PD...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12931-022-02201-8 |
| _version_ | 1797984611383377920 |
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| author | Fangqiu Fu Chaoqiang Deng Wenrui Sun Qiang Zheng Yan Jin Yuan Li Yang Zhang Haiquan Chen |
| author_facet | Fangqiu Fu Chaoqiang Deng Wenrui Sun Qiang Zheng Yan Jin Yuan Li Yang Zhang Haiquan Chen |
| author_sort | Fangqiu Fu |
| collection | DOAJ |
| description | Abstract Background Currently, programmed death ligand-1 (PD-L1) expression has been widely applied in clinical trials and real-world clinical practice as a major biomarker for the efficacy of immune-checkpoint inhibitors. The purpose of this study is to reveal the distribution and concordance of PD-L1 expression in a large-scale consecutive cohort from East-Asian patients with non-small cell lung cancer (NSCLC). Methods PD-L1 testing was conducted using 22C3 assays, and cases were categorized into the high, low, and no expression of PD-L1 based on the tumor proportion score (TPS). Target-capture next-generation sequencing was used to identify molecular events. Results A total of 4550 patients and 4622 tests of PD-L1 expression were enrolled. There were 3017 (66.3%) patients with no PD-L1 expression (TPS < 1%), 1013 (22.3%) with low PD-L1 expression (TPS 1–49%), 520 (11.4%) with high PD-L1 expression (TPS ≥ 50%). Higher proportions of positive PD-L1 expression (TPS ≥ 1%) were observed in smokers, males, squamous cell carcinoma, and high-grade lung adenocarcinoma. Further analyses revealed fair agreement in primary and metastatic lesions (kappa = 0.533), poor agreement in multi-focal primary tumors (kappa = 0.045), and good agreement in biopsy and resection samples (kappa = 0.662) / two biopsy samples (kappa = 0.711). Mutational analyses revealed association between high PD-L1 expression (TPS ≥ 50%) and EGFR wild-type, KRAS mutation, ALK rearrangement, and TP53 mutation. Conclusion The study reveals the unique distribution pattern of PD-L1 expression in a large-scale East-Asian cohort with NSCLC, the concordance of multiple PD-L1 tests, and the association between PD-L1 expression and molecular events. The results shed a light on the optimization of PD-L1 testing in clinical practice. |
| first_indexed | 2024-04-11T07:05:38Z |
| format | Article |
| id | doaj.art-5eeb4dd6a13840a9a9e6839c625d9dde |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-04-11T07:05:38Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-5eeb4dd6a13840a9a9e6839c625d9dde2022-12-22T04:38:25ZengBMCRespiratory Research1465-993X2022-11-0123111010.1186/s12931-022-02201-8Distribution and concordance of PD-L1 expression by routine 22C3 assays in East-Asian patients with non-small cell lung cancerFangqiu Fu0Chaoqiang Deng1Wenrui Sun2Qiang Zheng3Yan Jin4Yuan Li5Yang Zhang6Haiquan Chen7Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer CenterDepartment of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer CenterDepartment of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer CenterInstitute of Thoracic Oncology, Fudan UniversityInstitute of Thoracic Oncology, Fudan UniversityInstitute of Thoracic Oncology, Fudan UniversityDepartment of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer CenterDepartment of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer CenterAbstract Background Currently, programmed death ligand-1 (PD-L1) expression has been widely applied in clinical trials and real-world clinical practice as a major biomarker for the efficacy of immune-checkpoint inhibitors. The purpose of this study is to reveal the distribution and concordance of PD-L1 expression in a large-scale consecutive cohort from East-Asian patients with non-small cell lung cancer (NSCLC). Methods PD-L1 testing was conducted using 22C3 assays, and cases were categorized into the high, low, and no expression of PD-L1 based on the tumor proportion score (TPS). Target-capture next-generation sequencing was used to identify molecular events. Results A total of 4550 patients and 4622 tests of PD-L1 expression were enrolled. There were 3017 (66.3%) patients with no PD-L1 expression (TPS < 1%), 1013 (22.3%) with low PD-L1 expression (TPS 1–49%), 520 (11.4%) with high PD-L1 expression (TPS ≥ 50%). Higher proportions of positive PD-L1 expression (TPS ≥ 1%) were observed in smokers, males, squamous cell carcinoma, and high-grade lung adenocarcinoma. Further analyses revealed fair agreement in primary and metastatic lesions (kappa = 0.533), poor agreement in multi-focal primary tumors (kappa = 0.045), and good agreement in biopsy and resection samples (kappa = 0.662) / two biopsy samples (kappa = 0.711). Mutational analyses revealed association between high PD-L1 expression (TPS ≥ 50%) and EGFR wild-type, KRAS mutation, ALK rearrangement, and TP53 mutation. Conclusion The study reveals the unique distribution pattern of PD-L1 expression in a large-scale East-Asian cohort with NSCLC, the concordance of multiple PD-L1 tests, and the association between PD-L1 expression and molecular events. The results shed a light on the optimization of PD-L1 testing in clinical practice.https://doi.org/10.1186/s12931-022-02201-8PD-L1Non-small cell lung cancerDistributionConcordance |
| spellingShingle | Fangqiu Fu Chaoqiang Deng Wenrui Sun Qiang Zheng Yan Jin Yuan Li Yang Zhang Haiquan Chen Distribution and concordance of PD-L1 expression by routine 22C3 assays in East-Asian patients with non-small cell lung cancer Respiratory Research PD-L1 Non-small cell lung cancer Distribution Concordance |
| title | Distribution and concordance of PD-L1 expression by routine 22C3 assays in East-Asian patients with non-small cell lung cancer |
| title_full | Distribution and concordance of PD-L1 expression by routine 22C3 assays in East-Asian patients with non-small cell lung cancer |
| title_fullStr | Distribution and concordance of PD-L1 expression by routine 22C3 assays in East-Asian patients with non-small cell lung cancer |
| title_full_unstemmed | Distribution and concordance of PD-L1 expression by routine 22C3 assays in East-Asian patients with non-small cell lung cancer |
| title_short | Distribution and concordance of PD-L1 expression by routine 22C3 assays in East-Asian patients with non-small cell lung cancer |
| title_sort | distribution and concordance of pd l1 expression by routine 22c3 assays in east asian patients with non small cell lung cancer |
| topic | PD-L1 Non-small cell lung cancer Distribution Concordance |
| url | https://doi.org/10.1186/s12931-022-02201-8 |
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