Dataset Information

PD-L1 expression in malignant pleural effusion samples and its correlation with oncogene mutations in non-small cell lung cancer.

ABSTRACT:

Background

Programmed death ligand 1 (PD-L1) tumor proportion score (TPS) is currently widely used for selection of immune therapies in non-small cell lung cancer (NSCLC). Most of samples for PD-L1 expression were obtained from tumor tissue. However, the feasible of malignant pleural effusion (MPE) cytological samples for PD-L1 detection is poorly reported. And the correlation between oncogene mutations and PD-L1 expression based on high-throughput sequencing is rarely studied.

Methods

NSCLC MPE cytological samples and partially paired tumor tissue from our institution analyzed for PD-L1 immunohistochemistry (IHC) using the clone SP263 pharmDx kit and evaluated genomic aberrations in all patients using next generation sequencing (NGS).

Results

One hundred and twenty-three MPE cell blocks and 29 paired tumor tissue were successfully tested for PD-L1 expression. PD-L1 TPS of ≥50% were seen in 18.7% (23/123) of all samples. The accordance of PD-L1 expression in tumor tissue and MPE samples was 86.2% (50% as cut-off value). PD-L1 TPS ≥50% tumors were significantly associated with EGFR wild-type (P=0.007), but, no correlation between other genes and PD-L1 expression. A trend of longer overall survival (OS) was observed in patients with PD-L1 TPS <50% than those TPS ≥50% (20.0 vs. 13.8 months, P=0.057). No difference of tumor mutational burden (TMB) was observed between patients with PD-L1 ≥50% and <50% (8.2/MB and 7.7/MB, P=0.47).

Conclusions

Our results suggest that cytological material is feasible for PD-L1 IHC analysis. Gene alterations could partially contribute to select the samples that with different PD-L1 expression. No correlation between the PD-L1 expression and TMB.

SUBMITTER: Song Z

PROVIDER: S-EPMC7212145 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

PD-L1 expression in malignant pleural effusion samples and its correlation with oncogene mutations in non-small cell lung cancer.

Song Zhengbo Z Cheng Guoping G Zhang Yiping Y

Journal of thoracic disease 20200401 4

<h4>Background</h4>Programmed death ligand 1 (PD-L1) tumor proportion score (TPS) is currently widely used for selection of immune therapies in non-small cell lung cancer (NSCLC). Most of samples for PD-L1 expression were obtained from tumor tissue. However, the feasible of malignant pleural effusion (MPE) cytological samples for PD-L1 detection is poorly reported. And the correlation between oncogene mutations and PD-L1 expression based on high-throughput sequencing is rarely studied.<h4>Method ...[more]

PMID: 32395276

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Project description:The effects of non-amplification short variant (SV) mutations in CD274 (programmed death-ligand 1 (PD-L1)) on PD-L1 protein expression and immune checkpoint inhibitors (ICPIs) therapy are unknown. Here, we present a retrospective analysis of CD274 mutations detected by comprehensive genomic profiling (CGP) and correlate these results with tumor-cell PD-L1 immunohistochemistry (IHC)-based expression assessment to better understand the relationship between mutations and protein expression of PD-L1. CGP was performed on hybridization-captured, adaptor ligation-based libraries using DNA and/or RNA extracted from 314,631 tumor samples that were sequenced for up to 406 cancer-related genes and select gene rearrangements. PD-L1 IHC was performed on a subset of cases (n=58,341) using the DAKO 22C3 PD-L1 IHC assay and scored with the tumor proportion score (TPS). Overall, the prevalence of CD274 SV mutations was low (0.3%, 1081/314,631) with 577 unique variants. The most common CD274 SV mutations were R260H (n=51), R260C (n=18), R125Q (n=12), C272fs*13 (n=11), R86W (n=10), and R113H (n=10). The prevalence of CD274 mutations varied depending on tumor type with diffuse large B-cell lymphoma (1.9%, 19/997), cutaneous squamous cell carcinoma (1.6%, 14/868), endometrial adenocarcinoma (1.0%, 36/3740), unknown primary melanoma (0.9%, 33/3679), and cutaneous melanoma (0.8%, 32/3874) having the highest frequency of mutations. Of the R260H cases concurrently tested with PD-L1 IHC, most (81.8%, 9/11) had no PD-L1 expression, which contrasts to the five E237K cases where most (80%, 4/5) had PD-L1 expression. In addition, we saw a significantly lower level of PD-L1 expression in samples with a clonal truncating variant (nonsense or frameshift indel) when compared with samples with a subclonal truncating variants (mean: TPS=1 vs TPS=38; p<0.001), and also in clonal versus subclonal missense mutations (mean: TPS=11 vs TPS=22, respectively; p=0.049) CONCLUSIONS: We defined the landscape of CD274 mutations in a large cohort of tumor types that can be used as a reference for examining CD274 mutations as potential resistance biomarkers for ICPI. Furthermore, we presented novel data on the correlation of CD274 mutations and PD-L1 protein expression, providing important new information on the potential functionality of these mutations and can serve as a basis for future research.

Project description:Background: Programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) immune checkpoint inhibitors have been approved for monotherapy of metastatic nonsmall cell lung cancer (mNSCLC) depending on tumour cells' PD-L1 expression. Pleural effusion is common in mNSCLC. The significance of immunocytochemistry PD-L1 analysis from pleural effusion samples is unclear. Aim: The aim of the study was to analyse the sensitivity regarding immunocytochemistry PD-L1 analysis of pleural effusion in NSCLC as compared to immunohistochemistry of pleural biopsies. Patients and Methods: Fifty consecutive subjects (17 female, median age 72.5 years, seven never-smokers) were enrolled in this prospective controlled two-centre study. Inclusion criteria were pleural effusion, suspected or known lung cancer, indication for pleural puncture and thoracoscopy, and written informed consent. Immunocytochemistry and immunohistochemistry PD-L1 analyses were performed with the Dako-PDL1-IHC-22C3pharmDx assay. Analysis for sensitivity, specificity, and positive and negative predictive value was performed for PD-L1 detection from pleural effusion. Results: 50 subjects underwent pleural puncture and thoracoscopy. Pathological diagnoses were lung cancer (48), lymphoma (1) and mesothelioma (1). Sensitivity, specificity, positive predictive value and negative predictive value of PD-L1-testing with expression ≥50% defined as positive were 100% (95% CI 46-100%), 63% (36-84%), 45% (18-75%) and 100% (66-100%), and with expression ≥1% defined as positive 86% (56-97%), 43% (12-80%), 75% (47-92%) and 60% (17-93%). Conclusion: PD-L1 analysis in tumour-positive pleural effusion samples shows a very high sensitivity and negative predictive value, especially regarding PD-L1 expression levels ≥50% (European Medicines Agency approval). Negative results are reliable and help in the decision against a first-line checkpoint inhibitor monotherapy. However, a 1% cut-off level (United States Food and Drug Administration approval) leads to a markedly lower negative predictive value, making other invasive procedures necessary (NCT02855281).

Dataset Information

PD-L1 expression in malignant pleural effusion samples and its correlation with oncogene mutations in non-small cell lung cancer.

Background

Methods

Results

Conclusions

Publications

PD-L1 expression in malignant pleural effusion samples and its correlation with oncogene mutations in non-small cell lung cancer.

Similar Datasets

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