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Association of PD-L1 expression and PD-L1 gene polymorphism with poor prognosis in lung adenocarcinoma and squamous cell carcinoma

Programmed cell death 1 receptor (PD-1)/programmed death-1 ligand-1 (PD-L1) interaction has been linked to tumor immune evasion. PD-L1 expression has been indicated in identifying non–small cell lung carcinoma (NSCLC) patients for treatment with anti–PD-1 or anti–PD-L1 therapy. The goal of this stud...

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Published in:Human pathology 2017-10, Vol.68, p.103-111
Main Authors: Yeo, Min-Kyung, Choi, Song-Yi, Seong, In-Ock, Suh, Kwang-Sun, Kim, Jin Man, Kim, Kyung-Hee
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container_title Human pathology
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description Programmed cell death 1 receptor (PD-1)/programmed death-1 ligand-1 (PD-L1) interaction has been linked to tumor immune evasion. PD-L1 expression has been indicated in identifying non–small cell lung carcinoma (NSCLC) patients for treatment with anti–PD-1 or anti–PD-L1 therapy. The goal of this study was to evaluate the clinicopathologic values of PD-L1 expression and single-nucleotide polymorphisms (SNPs) in the PD-L1 gene in lung adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). The 147 NSCLC tissues consisted of 84 samples of ADC and 63 samples of SqCC. All tissue microarray paraffin blocks were used for PD-L1 immunohistochemical assays with 22C3, SP263, and SP142 clones. Three SNPs in the PD-L1 gene, rs4143815, rs822336, and rs822337, were genotyped using SNP pyrosequencing. The PD-L1 expression was significantly higher in SqCC than in ADC. Among ADCs, PD-L1 expression was significantly higher in papillary and solid types than in lepidic and acinar types. Statistical associations of the PD-L1 expression with a shorter disease-free survival outcome and lymph node metastasis in the ADCs were found but no associations in SqCCs. Among the three SNPs, the rs4143815 genotype CC was statistically associated with positive 22C3 PD-L1 labeling in NSCLCs. The rs4143815 genotype GG instead showed a trend of shorter survival outcomes but did not reach statistical significance in the ADCs. Our results showed a significantly higher prevalence of positive PD-L1 expression in lung SqCC than in ADC. However, the PD-L1 expression and rs4143815 genotype GG might be useful for the prediction of poor prognosis in lung ADC cases. •147 cases of non–small cell lung carcinoma were studied.•Positive PD-L1 expression was associated with poor prognosis in adenocarcinoma.•The rs4143815 genotype GG showed a trend of poor prognosis in adenocarcinoma.•The rs4143815 genotype CC was associated with PD-L1 expression.
doi_str_mv 10.1016/j.humpath.2017.08.016
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PD-L1 expression has been indicated in identifying non–small cell lung carcinoma (NSCLC) patients for treatment with anti–PD-1 or anti–PD-L1 therapy. The goal of this study was to evaluate the clinicopathologic values of PD-L1 expression and single-nucleotide polymorphisms (SNPs) in the PD-L1 gene in lung adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). The 147 NSCLC tissues consisted of 84 samples of ADC and 63 samples of SqCC. All tissue microarray paraffin blocks were used for PD-L1 immunohistochemical assays with 22C3, SP263, and SP142 clones. Three SNPs in the PD-L1 gene, rs4143815, rs822336, and rs822337, were genotyped using SNP pyrosequencing. The PD-L1 expression was significantly higher in SqCC than in ADC. Among ADCs, PD-L1 expression was significantly higher in papillary and solid types than in lepidic and acinar types. Statistical associations of the PD-L1 expression with a shorter disease-free survival outcome and lymph node metastasis in the ADCs were found but no associations in SqCCs. Among the three SNPs, the rs4143815 genotype CC was statistically associated with positive 22C3 PD-L1 labeling in NSCLCs. The rs4143815 genotype GG instead showed a trend of shorter survival outcomes but did not reach statistical significance in the ADCs. Our results showed a significantly higher prevalence of positive PD-L1 expression in lung SqCC than in ADC. However, the PD-L1 expression and rs4143815 genotype GG might be useful for the prediction of poor prognosis in lung ADC cases. •147 cases of non–small cell lung carcinoma were studied.•Positive PD-L1 expression was associated with poor prognosis in adenocarcinoma.•The rs4143815 genotype GG showed a trend of poor prognosis in adenocarcinoma.•The rs4143815 genotype CC was associated with PD-L1 expression.</description><identifier>ISSN: 0046-8177</identifier><identifier>EISSN: 1532-8392</identifier><identifier>DOI: 10.1016/j.humpath.2017.08.016</identifier><identifier>PMID: 28851662</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adenocarcinoma ; Adenocarcinoma - genetics ; Adenocarcinoma - immunology ; Adenocarcinoma - secondary ; Adenocarcinoma - surgery ; Adenocarcinoma of Lung ; Adult ; Aged ; Aged, 80 and over ; Apoptosis ; B7-H1 Antigen - analysis ; B7-H1 Antigen - genetics ; Biomarkers, Tumor - analysis ; Biomarkers, Tumor - genetics ; Cancer therapies ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - immunology ; Carcinoma, Non-Small-Cell Lung - secondary ; Carcinoma, Non-Small-Cell Lung - surgery ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - immunology ; Carcinoma, Squamous Cell - secondary ; Carcinoma, Squamous Cell - surgery ; Cell death ; Cloning ; Deoxyribonucleic acid ; Disease-Free Survival ; DNA ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Homozygote ; Hospitals ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Ligands ; Lung cancer ; Lung Neoplasms - genetics ; Lung Neoplasms - immunology ; Lung Neoplasms - pathology ; Lung Neoplasms - surgery ; Lymphatic Metastasis ; Male ; Medical prognosis ; Middle Aged ; Non–small cell lung carcinoma ; Phenotype ; Polymorphism, Single Nucleotide ; Programmed cell death 1 receptor ; Programmed death-1 ligand-1 ; Proportional Hazards Models ; Protein expression ; Proteins ; Retrospective Studies ; Single-nucleotide polymorphism ; Squamous cell carcinoma ; Survival analysis ; Time Factors ; Tissue Array Analysis</subject><ispartof>Human pathology, 2017-10, Vol.68, p.103-111</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. 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PD-L1 expression has been indicated in identifying non–small cell lung carcinoma (NSCLC) patients for treatment with anti–PD-1 or anti–PD-L1 therapy. The goal of this study was to evaluate the clinicopathologic values of PD-L1 expression and single-nucleotide polymorphisms (SNPs) in the PD-L1 gene in lung adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). The 147 NSCLC tissues consisted of 84 samples of ADC and 63 samples of SqCC. All tissue microarray paraffin blocks were used for PD-L1 immunohistochemical assays with 22C3, SP263, and SP142 clones. Three SNPs in the PD-L1 gene, rs4143815, rs822336, and rs822337, were genotyped using SNP pyrosequencing. The PD-L1 expression was significantly higher in SqCC than in ADC. Among ADCs, PD-L1 expression was significantly higher in papillary and solid types than in lepidic and acinar types. 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PD-L1 expression has been indicated in identifying non–small cell lung carcinoma (NSCLC) patients for treatment with anti–PD-1 or anti–PD-L1 therapy. The goal of this study was to evaluate the clinicopathologic values of PD-L1 expression and single-nucleotide polymorphisms (SNPs) in the PD-L1 gene in lung adenocarcinoma (ADC) and squamous cell carcinoma (SqCC). The 147 NSCLC tissues consisted of 84 samples of ADC and 63 samples of SqCC. All tissue microarray paraffin blocks were used for PD-L1 immunohistochemical assays with 22C3, SP263, and SP142 clones. Three SNPs in the PD-L1 gene, rs4143815, rs822336, and rs822337, were genotyped using SNP pyrosequencing. The PD-L1 expression was significantly higher in SqCC than in ADC. Among ADCs, PD-L1 expression was significantly higher in papillary and solid types than in lepidic and acinar types. Statistical associations of the PD-L1 expression with a shorter disease-free survival outcome and lymph node metastasis in the ADCs were found but no associations in SqCCs. Among the three SNPs, the rs4143815 genotype CC was statistically associated with positive 22C3 PD-L1 labeling in NSCLCs. The rs4143815 genotype GG instead showed a trend of shorter survival outcomes but did not reach statistical significance in the ADCs. Our results showed a significantly higher prevalence of positive PD-L1 expression in lung SqCC than in ADC. However, the PD-L1 expression and rs4143815 genotype GG might be useful for the prediction of poor prognosis in lung ADC cases. •147 cases of non–small cell lung carcinoma were studied.•Positive PD-L1 expression was associated with poor prognosis in adenocarcinoma.•The rs4143815 genotype GG showed a trend of poor prognosis in adenocarcinoma.•The rs4143815 genotype CC was associated with PD-L1 expression.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28851662</pmid><doi>10.1016/j.humpath.2017.08.016</doi><tpages>9</tpages></addata></record>
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subjects Adenocarcinoma
Adenocarcinoma - genetics
Adenocarcinoma - immunology
Adenocarcinoma - secondary
Adenocarcinoma - surgery
Adenocarcinoma of Lung
Adult
Aged
Aged, 80 and over
Apoptosis
B7-H1 Antigen - analysis
B7-H1 Antigen - genetics
Biomarkers, Tumor - analysis
Biomarkers, Tumor - genetics
Cancer therapies
Carcinoma, Non-Small-Cell Lung - genetics
Carcinoma, Non-Small-Cell Lung - immunology
Carcinoma, Non-Small-Cell Lung - secondary
Carcinoma, Non-Small-Cell Lung - surgery
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - immunology
Carcinoma, Squamous Cell - secondary
Carcinoma, Squamous Cell - surgery
Cell death
Cloning
Deoxyribonucleic acid
Disease-Free Survival
DNA
Female
Gene Expression Regulation, Neoplastic
Genetic Predisposition to Disease
Homozygote
Hospitals
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Ligands
Lung cancer
Lung Neoplasms - genetics
Lung Neoplasms - immunology
Lung Neoplasms - pathology
Lung Neoplasms - surgery
Lymphatic Metastasis
Male
Medical prognosis
Middle Aged
Non–small cell lung carcinoma
Phenotype
Polymorphism, Single Nucleotide
Programmed cell death 1 receptor
Programmed death-1 ligand-1
Proportional Hazards Models
Protein expression
Proteins
Retrospective Studies
Single-nucleotide polymorphism
Squamous cell carcinoma
Survival analysis
Time Factors
Tissue Array Analysis
title Association of PD-L1 expression and PD-L1 gene polymorphism with poor prognosis in lung adenocarcinoma and squamous cell carcinoma
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