PD-L1 immunohistochemistry in non-small-cell lung cancer: unraveling differences in staining concordance and interpretation

Keppens, Cleo; Dequeker, Elisabeth; Pauwels, Patrick; Ryška, Aleš; Hart, Nils ’t; Thüsen, Jan H. von der

doi:10.1007/s00428-020-02976-5

Cited by 11 publications

(6 citation statements)

References 27 publications

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“…While the former is largely unpredictable, the latter should be standardized by following strict laboratory protocols [167]. However, differences in staining concordance and interpretation may occur among various institutes [166,174]. Recently, Angels et al [175] reported a significant rate of suboptimal PD-L1 immunostaining (clones SP142 and SP263) in tonsillectomy specimens exposed to more than 72 h in formaldehyde.…”

Section: Discussionmentioning

confidence: 99%

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 1: Focus on Immunohistochemical Results with Discussion of Pre-Analytical and Interpretation Variables

Palicelli

Bonacini

Croci

et al. 2021

Cells

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Immunotherapy targeting the PD-1–PD-L1 axis yielded good results in treating different immunologically ‘‘hot’’ tumors. A phase II study revealed good therapeutic activity of pembrolizumab in selected prostatic carcinoma (PC)-patients. We performed a systematic literature review (PRISMA guidelines), which analyzes the immunohistochemical expression of PD-L1 in human PC samples and highlights the pre-analytical and interpretation variables. Interestingly, 29% acinar PCs, 7% ductal PCs, and 46% neuroendocrine carcinomas/tumors were PD-L1+ on immunohistochemistry. Different scoring methods or cut-off criteria were applied on variable specimen-types, evaluating tumors showing different clinic-pathologic features. The positivity rate of different PD-L1 antibody clones in tumor cells ranged from 3% (SP142) to 50% (ABM4E54), excluding the single case tested for RM-320. The most tested clone was E1L3N, followed by 22C3 (most used for pembrolizumab eligibility), SP263, SP142, and 28-8, which gave the positivity rates of 35%, 11–41% (depending on different scoring systems), 6%, 3%, and 15%, respectively. Other clones were tested in <200 cases. The PD-L1 positivity rate was usually higher in tumors than benign tissues. It was higher in non-tissue microarray specimens (41–50% vs. 15%), as PC cells frequently showed heterogenous or focal PD-L1-staining. PD-L1 was expressed by immune or stromal cells in 12% and 69% cases, respectively. Tumor heterogeneity, inter-institutional preanalytics, and inter-observer interpretation variability may account for result biases.

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Section: Discussionmentioning

confidence: 99%

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 1: Focus on Immunohistochemical Results with Discussion of Pre-Analytical and Interpretation Variables

Palicelli

Bonacini

Croci

et al. 2021

Cells

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“…We do not know how many of the laboratories included in our study participated in PD-L1 external quality assessment (EQA) schemes during the study period. Potentially, participation of all laboratories in such EQA schemes could help in reducing interlaboratory variation in PD-L1 positivity [48]. Also, when LDTs are used for PD-L1 staining, it is paramount that these LDTs are optimized and validated sufficiently [49].…”

Section: Discussionmentioning

confidence: 99%

Considerable interlaboratory variation in PD-L1 positivity in a nationwide cohort of non-small cell lung cancer patients

Koomen

Voorham²,

Epskamp-Kuijpers

et al. 2021

Lung Cancer

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Immunohistochemical expression of programmed death-ligand 1 (PD-L1) is used as a predictive biomarker for prescription of immunotherapy to non-small cell lung cancer (NSCLC) patients. Accurate assessment of PD-L1 expression is therefore crucial. In this study, the extent of interlaboratory variation in PD-L1 positivity in the Netherlands was assessed, using real-world clinical pathology data. Materials and Methods: Data on all NSCLC patients in the Netherlands with a mention of PD-L1 testing in their pathology report from July 2017 to December 2018 were extracted from PALGA, the nationwide network and registry of histo-and cytopathology in the Netherlands. PD-L1 positivity rates were determined for each laboratory that performed PD-L1 testing, with separate analyses for histological and cytological material. Two cutoffs (1% and 50%) were used to determine PD-L1 positivity. Differences between laboratories were assessed using funnel plots with 95% confidence limits around the overall mean. Results: 6,354 patients from 30 laboratories were included in the analysis of histology data. At the 1% cutoff, maximum interlaboratory variation was 39.1% (32.7%− 71.8%) and ten laboratories (33.3%) differed significantly from the mean. Using the 50% cutoff, four laboratories (13.3%) differed significantly from the mean and maximum variation was 23.1% (17.2%− 40.3%). In the analysis of cytology data, 1,868 patients from 23 laboratories were included. Eight laboratories (34.8%) differed significantly from the mean in the analyses of both cutoffs. Maximum variation was 41.2% (32.2%− 73.4%) and 29.2% (14.7%− 43.9%) using the 1% and 50% cutoffs, respectively. Conclusion: Considerable interlaboratory variation in PD-L1 positivity was observed. Variation was largest using the 1% cutoff. At the 50% cutoff, analysis of cytology data demonstrated a higher degree of variation than the analysis of histology data.

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“…Overall, the use of commercial kits results in a better staining performance compared to LDTs [ 16 , 56 ]. Nonetheless, essential for an optimal staining score is a validated protocol obtaining a good staining quality, while paying attention to interpretation competence of the pathologist to reduce inter-individual variation and avoiding misclassification/misinterpretation [ 15 , 16 , 57 , 58 ]. In addition, accreditation also had a positive impact on staining performance and interpretation for these biomarkers [ 55 ].…”

Section: The Scientific Value Of Eqa Schemes and Importance For Indus...mentioning

confidence: 99%

“…In addition, EQA has proven its benefit for by creating the opportunity to set up collaborations with the EQA provider to investigate the use and performance of their kits. Previous EQA research has shown that EQA participation can reveal flaws in testing methods, for example essential differences between staining techniques [ 15 , 16 ]. In addition, EQA schemes, as well as ring studies, have had a supporting role in the development of best practice guidelines by highlighting pitfalls and common errors [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

The Significance of External Quality Assessment Schemes for Molecular Testing in Clinical Laboratories

Laudus

Nijs

Nauwelaers

et al. 2022

Cancers

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External quality assessment (EQA) schemes are a tool for clinical laboratories to evaluate and manage the quality of laboratory practice with the support of an independent party (i.e., an EQA provider). Depending on the context, there are different types of EQA schemes available, as well as various EQA providers, each with its own field of expertise. In this review, an overview of the general requirements for EQA schemes and EQA providers based on international guidelines is provided. The clinical and scientific value of these kinds of schemes for clinical laboratories, clinicians and patients are highlighted, in addition to the support EQA can provide to other types of laboratories, e.g., laboratories affiliated to biotech companies. Finally, recent developments and challenges in laboratory medicine and quality management, for example, the introduction of artificial intelligence in the laboratory and the shift to a more individual-approach instead of a laboratory-focused approach, are discussed. EQA schemes should represent current laboratory practice as much as possible, which poses the need for EQA providers to introduce latest laboratory innovations in their schemes and to apply up-to-date guidelines. By incorporating these state-of-the-art techniques, EQA aims to contribute to continuous learning.

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PD-L1 immunohistochemistry in non-small-cell lung cancer: unraveling differences in staining concordance and interpretation

Cited by 11 publications

References 27 publications

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 1: Focus on Immunohistochemical Results with Discussion of Pre-Analytical and Interpretation Variables

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 1: Focus on Immunohistochemical Results with Discussion of Pre-Analytical and Interpretation Variables

Considerable interlaboratory variation in PD-L1 positivity in a nationwide cohort of non-small cell lung cancer patients

The Significance of External Quality Assessment Schemes for Molecular Testing in Clinical Laboratories

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