scholarly journals Multicentric analytical comparability study of programmed death-ligand 1 expression on tumor-infiltrating immune cells and tumor cells in urothelial bladder cancer using four clinically developed immunohistochemistry assays

2019 ◽  
Vol 475 (5) ◽  
pp. 599-608 ◽  
Author(s):  
Kristina Schwamborn ◽  
Johannes U Ammann ◽  
Ruth Knüchel ◽  
Arndt Hartmann ◽  
Gustavo Baretton ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Tumor Cells ◽  
Immune Cells ◽  
Urothelial Bladder Cancer ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Urothelial Bladder

scholarly journals Programmed Death Ligand-1 (PD-L1) Expression in Either Tumor Cells or Tumor-Infiltrating Immune Cells Correlates With Solid and High-Grade Lung Adenocarcinomas

2017 ◽  
Vol 141 (11) ◽  
pp. 1529-1532 ◽  
Author(s):  
Brandon R. Driver ◽  
Ross A. Miller ◽  
Tara Miller ◽  
Michael Deavers ◽  
Blythe Gorman ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Immune Cells ◽  
Histologic Grade ◽  
Fisher Exact Test ◽  
Clinicopathologic Features ◽  
Cell Lung Carcinoma ◽  
Programmed Death Ligand 1 ◽  
Exact Test ◽  
Programmed Death ◽  
High Histologic Grade

Context.— Programmed death ligand-1 (PD-L1) expression in non–small cell lung carcinoma (NSCLC) is heterogeneous and known to be underestimated on small biopsies. Correlation of PD-L1 expression with clinicopathologic features may provide additional useful information. To our knowledge, the clinicopathologic features of NSCLC have not been reported for subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells. Objective.— To investigate the clinicopathologic characteristics of NSCLC subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells. Design.— PD-L1 immunohistochemistry with the SP142 clone was performed on whole-tissue sections and given semiquantitative scores (0/1/2/3) according to percent of PD-L1+ tumor cells (TCs) and percent tumor area with PD-L1+ tumor-infiltrating immune cells (ICs). Results.— Adenocarcinoma cases that were scored either TC 1/2/3 or IC 1/2/3 included most (22 of 34; 65%) high–histologic grade cases and most (25 of 36; 69%) solid subtype cases. Compared with the adenocarcinoma TC 0 and IC 0 subset, the TC 1/2/3 or IC 1/2/3 subset correlated with higher histologic grade (P = .005, χ2 test for trend) and solid subtype (P < .001, Fisher exact test). Compared with the adenocarcinoma TC 0/1 or IC 0/1 subset, the TC 2/3 or IC 2/3 subset correlated with higher histologic grade (P = .002, χ2 test for trend), solid subtype (P < .001, Fisher exact test), and higher smoking pack-years (P = .01, Mann-Whitney test). Conclusions.— Lung adenocarcinoma subsets defined by PD-L1 expression in either tumor cells or tumor-infiltrating immune cells correlated with high histologic grade, solid subtype, and high smoking pack-years.

scholarly journals Emergence of undifferentiated urothelial carcinoma after pembrolizumab treatment for patient with invasive urothelial bladder cancer: A case report

2020 ◽  
Vol 8 ◽  
pp. 2050313X2093269
Author(s):  
Moto Hasegawa ◽  
Go Hasegawa ◽  
Yohei Ikeda ◽  
Noboru Hara ◽  
Tsutomu Nishiyama
Keyword(s):  
Bladder Cancer ◽  
Urothelial Carcinoma ◽  
Tumor Tissue ◽  
Pathological Findings ◽  
Urothelial Bladder Cancer ◽  
Squamous Differentiation ◽  
Small Tumor ◽  
Anticancer Chemotherapy ◽  
Programmed Death ◽  
Urothelial Bladder

An 83-year-old man received pembrolizumab treatment after anticancer chemotherapy with gemcitabine and cisplatin for advanced bladder cancer. Pathological findings revealed invasive urothelial carcinoma with squamous differentiation before treatment. After seven courses of pembrolizumab treatment, the tumor disappeared. After 15 courses of the treatment, the tumor regrew. Pathological findings revealed invasive undifferentiated urothelial carcinoma consisting of relatively small tumor cells of the same size as lymphocytes, negative for neuroendocrine markers. Programmed death-ligand 1 expressions in tumor tissue changed from positive before treatment to negative after pembrolizumab treatment.

scholarly journals Analytical Validation and Clinical Utility of an Immunohistochemical Programmed Death Ligand-1 Diagnostic Assay and Combined Tumor and Immune Cell Scoring Algorithm for Durvalumab in Urothelial Carcinoma

2018 ◽  
Vol 143 (6) ◽  
pp. 722-731 ◽  
Author(s):  
Magdalena Zajac ◽  
Anne-Marie Boothman ◽  
Yong Ben ◽  
Ashok Gupta ◽  
Xiaoping Jin ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Tumor Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Objective Response ◽  
Clinical Activity ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Sensitivity Specificity ◽  
Tumor Area

Context.— Clinical responses to anti–programmed death receptor-1 and anti–programmed death ligand-1 (PD-L1) agents are generally improved in patients with high PD-L1 expression compared with those with low/negative expression across several tumor types, including urothelial carcinoma. Objective.— To validate a PD-L1 immunohistochemical diagnostic test in urothelial carcinoma patients treated with the anti–PD-L1 monoclonal antibody durvalumab. Design.— The Ventana PD-L1 (SP263) assay was validated for intended use in urothelial carcinoma formalin-fixed, paraffin-embedded samples in studies addressing sensitivity, specificity, robustness, and precision, and implemented in study CD-ON-MEDI4736-1108 (NCT01693562). Efficacy was analyzed in patients classified according to prespecified PD-L1 expression cutoffs: PD-L1 high (if >1% of the tumor area contained tumor-associated immune cells, ≥25% of tumor cells or ≥25% of immune cells stained for PD-L1; if ≤1% of the tumor area contained immune cells, ≥25% of tumor cells or 100% of immune cells stained for PD-L1) and PD-L1 low/negative (did not meet criteria for PD-L1 high). Results.— The assay met all predefined acceptance criteria for sensitivity, specificity, and precision. Interreader and intrareader precision overall agreement were 93.0% and 92.4%, respectively. For intraday reproducibility and interday precision, overall agreement was 99.2% and 100%, respectively. Interlaboratory overall agreement was 92.6%. In study CD-ON-MEDI4736-1108, durvalumab demonstrated clinical activity and durable responses in both PD-L1–high and PD-L1–low/negative subgroups, although objective response rates tended to be higher in the PD-L1–high subgroup than in the PD-L1–low/negative subgroup. Conclusions.— Determination of PD-L1 expression in urothelial carcinoma patients using the Ventana PD-L1 (SP263) assay was precise, highly reproducible, and clinically relevant.

scholarly journals PD-L1 expression in urothelial bladder cancer varies more among specimen types than between companion assays

2021 ◽  
Author(s):  
Joep J. de Jong ◽  
Hans Stoop ◽  
Joost L. Boormans ◽  
Geert J.L.H. van Leenders
Keyword(s):  
Bladder Cancer ◽  
Checkpoint Inhibitors ◽  
Urothelial Bladder Cancer ◽  
Future Studies ◽  
Expression Variability ◽  
Node Metastasis ◽  
Programmed Death ◽  
Platinum Based Chemotherapy ◽  
Scoring Algorithm ◽  
Urothelial Bladder

AbstractUrothelial bladder cancer (UBC) patients ineligible to platinum-based chemotherapy can be treated with immune-checkpoint inhibitors (ICI) in Programmed Death Ligand 1 (PD-L1) positive cases. Although concordance exists between different PD-L1 assays, little is known on PD-L1 expression variability in matched UBC samples. We compared PD-L1 expression in whole slides of matched transurethral resections (TURBT), radical cystectomies (RC), and lymph node metastasis (LN). Immunohistochemistry using the VENTANA PD-L1 (SP263) assay was performed on 115 patients and scored positive if expression occurred in ≥25% immune cells (IC), ≥25% tumour cells (TC), or both. PD-L1 was positive in 42.7% TURBT, 39.8% RC, and 27.3% LN specimens. Concordance was moderate (κ=0.52; P<0.001) between TURBT and RC, and fair between LN and TURBT (κ=0.31; P=0.048) or RC (κ=0.25; P=0.075). Comparison with the VENTANA PD-L1 (SP142) assay which had been performed previously on the same cohort showed moderate to substantial inter-assay agreement (κ=0.42–0.66). Although TC staining is not part of the SP142 scoring algorithm, discordant PD-L1 assay outcome could be attributed to SP263 TC≥25% staining in only 41% of cases. These results show that PD-L1 expression variability between matched specimens is higher than that between individual assays. Optimal specimen determination for PD-L1 testing needs to be addressed in future studies.

scholarly journals Optimal Evaluation of Programmed Death Ligand-1 on Tumor Cells Versus Immune Cells Requires Different Detection Methods

2018 ◽  
Vol 142 (8) ◽  
pp. 982-991 ◽  
Author(s):  
Kelly A. Schats ◽  
Emily A. Van Vré ◽  
Carolien Boeckx ◽  
Martine De Bie ◽  
Dorien M. Schrijvers ◽  
...  
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Detection Method ◽  
Death Receptor ◽  
Detection Methods ◽  
Programmed Death Ligand 1 ◽  
Cell Staining ◽  
Programmed Death

Context.— The benefit of programmed death ligand-1 (PD-L1) immunohistochemistry (IHC) as a method to select patients who may benefit from programmed death receptor-1 (PD-1)/PD-L1 immunotherapies remains uncertain in many tumor indications. Objectives.— To compare the commercially available, approved PD-L1 IHC assays (22C3, 28-8, SP142, SP263), specifically identifying the changes in staining output created by altering the detection method. Design.— This pilot study investigates the respective PD-L1 kit assay staining patterns and related scoring of tumor cells and immune cells on lung carcinoma and melanoma. Furthermore, the influence of the detection method (platform and related reagents) on PD-L1 antibody performance is studied. Results.— The SP142 kit reveals more immune cell staining but less tumor cell staining than the other PD-L1 kits. Alternatively, the 22C3 and 28-8 kits show good tumor cell sensitivity, but less pronounced immune cell staining, even in tonsil. Tumor cell staining by the SP263 kit is comparable to that of 22C3 and 28-8 kits, while immune cell staining is better. Strikingly, the selection of the detection method has a major impact on the sensitivity of the assay for PD-L1 detection per cell type. Switching the detection method of the kits could largely circumvent the observed staining differences. Conclusions.— The diverse sensitivities caused by the choice of the detection method should be taken into consideration when selecting PD-L1 kits or developing PD-L1 IHC laboratory-developed tests. When using alternative kits or laboratory-developed tests, it is strongly recommended to reestablish their clinical utility per therapeutic agent or compare them with the original kit.

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