Unique distribution of programmed death ligand 1 (PD-L1) expression in East Asian non-small cell lung cancer

Pan, Yunjian; Zheng, Deyou; Li, Yuan; Cai, Xu; Zheng, Zongli; Jin, Yan; Hu, Haichuan; Cheng, Chao; Shen, Lei; Wang, Jian; Ji, Hongbin; Sun, Yihua; Zhou, Xiaoyan; Chen, Haiquan

doi:10.21037/jtd.2017.08.61

Cited by 54 publications

(46 citation statements)

References 22 publications

(21 reference statements)

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“…In our study, solid and squamous areas were associated with higher PD‐L1 levels, both when comparing between tumours, and when comparing between histotype areas within tumours. The intertumoral aspect of this finding is consistent with prior studies showing that squamous cell carcinomas tended to have higher PD‐L1 levels than adenocarcinomas, and that predominantly solid adenocarcinomas tended to have higher PD‐L1 levels than other adenocarcinomas . Only a minority of the prior studies reported data at both of the clinically relevant thresholds (1% and 50%), and only a subset reported on each of the common adenocarcinoma subtypes .…”

Section: Discussionsupporting

confidence: 87%

“…Insights into the adequacy of a tumour block or biopsy sample for PD‐L1 testing may be gained through evaluation of histological features associated with PD‐L1 levels. Although there is no consensus in the literature, some studies have associated differences in PD‐L1 levels between tumours with differences in the architectural growth pattern, or histotype, of the tumours . As NSCLCs often have multiple different histotype areas, different PD‐L1 levels within a tumour may be associated with local variation in histotype.…”

Section: Introductionmentioning

confidence: 99%

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Intratumoral heterogeneity in programmed death‐ligand 1 immunoreactivity is associated with variation in non‐small cell lung carcinoma histotype

et al. 2019

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Aims Accurate assessment of programmed death‐ligand 1 (PD‐L1) levels in non‐small cell lung carcinoma (NSCLC) samples is complicated by intratumoral heterogeneity. We aimed to: (i) establish whether intratumoral PD‐L1 variation is associated with differences in local histotype; (ii) identify histotypes associated with a tendency for there to be higher or lower PD‐L1 scores; and (iii) estimate the frequency of clinically significant discordance in PD‐L1 levels between intratumoral histotype areas. Methods and results We reviewed 166 NSCLC resection specimens clinically tested for PD‐L1 with the 22C3 pharmDx assay. Multiple histotypes were present in 55% (68/123) of non‐mucinous adenocarcinoma samples. Solid histotypes had significantly higher PD‐L1 levels than other histotypes, both when samples were grouped by predominant histotype, and when histotype areas within a tumour were compared (P < 0.02). Lepidic areas had significantly lower PD‐L1 levels than other histotype areas within the same tumour (P < 0.02). Discordance between intratumoral histotype areas at a clinically relevant threshold (PD‐L1 tumour proportion score of 1% or 50%) was present in 32% (22/68) of non‐mucinous adenocarcinoma specimens with multiple histotype areas. The lepidic histotype was most frequently involved in discordance. Conclusions Intratumoral heterogeneity in PD‐L1 is associated with variation in histotype. Over‐representation of solid areas may increase the PD‐L1 score assigned to a tumour, whereas over‐representation of lepidic areas may decrease the PD‐L1 score. Evaluation of how histotype representation impacts on the predictive value of PD‐L1 testing is warranted.

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Section: Discussionsupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Intratumoral heterogeneity in programmed death‐ligand 1 immunoreactivity is associated with variation in non‐small cell lung carcinoma histotype

et al. 2019

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“…However, no consensus has been reached. In our study, we found that patients with lung AC were more likely to have PD-L1-positive tumors than patients with SCC, which was consistent with the results of a recent metaanalysis [37] but different from a report on East Asian populations [38]. Since most of the samples included in this study were AC, we cannot exclude the influence of the small sample size of SCC on the reliability of the results.…”

Section: Discussionsupporting

confidence: 81%

Cytology cell blocks from malignant pleural effusion are good candidates for PD-L1 detection in advanced NSCLC compared with matched histology samples

Zou

Tang

et al. 2020

BMC Cancer

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Background: Detection of programmed cell death ligand-1 (PD-L1) by immunohistochemistry (IHC) has been commonly used to predict the efficacy of treatment with PD-1/PD-L1 inhibitors. However, there is limited literature regarding the reliability of PD-L1 testing using malignant pleural effusion (MPE) cell blocks. Here, we assess PD-L1 expression in sections from MPE cell blocks and evaluate the value of IHC double staining in the interpretation of PD-L1 expression. Methods: In all, 124 paired formalin-fixed tissues from advanced NSCLC patients, including MPE cell blocks and matched histology samples, were included. PD-L1 expression was assessed using the SP263 assay, and the tumor proportion score (TPS) and the staining intensity were evaluated. PD-L1 staining results were also compared between IHC double and single staining techniques. Results: PD-L1 expression was concordant in most paired cases (86/101, 85.1%) among three TPS cutoffs (<1%, 1-49% and ≥ 50%), with a kappa value of 0.774. Moreover, a significant difference in PD-L1 expression between MPE cell blocks and biopsy samples was observed (p = 0.005). For the 15 discordant pairs, 13 MPE cell block samples showed increased expression of PD-L1. Compared with the standard IHC single PD-L1 assay, double staining with anti-TTF-1 and anti-PD-L1 revealed a negative effect on PD-L1 expression testing and resulted in weaker staining intensity and a lower TPS (p = 0.000). Conclusions: MPE cell block samples are good candidates for PD-L1 expression detection in advanced NSCLC patients. The mechanism and clinical significance of the higher PD-L1 expression rate in MPE cell blocks compared with small biopsy samples remain to be evaluated prospectively.

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“…No significant association was found between tumor size and PD-L1 expression among the subjects in the present study. This finding was contrary to that demonstrated by Yunjian P et al who found that there was a significant association between positive PD-L1 expression (including TPS ≥ 50% and TPS < 50%) in the ADC cohort with large tumor size [21]. Adenocarcinoma was the most common histological type of NSCLC in the current study.…”

Section: Discussioncontrasting

confidence: 99%

Correlation of Programmed Death Ligand-1 (PD-L1) Expression with Clinicopathological Features in Non-Small Cell Lung Carcinoma: Experience from a Tertiary Cancer Care Center in India

Saif¹,

Kumar²,

Mufti³

et al. 2020

JCT

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Background: According to the GLOBOCAN 2018 report, the estimated incidence of lung cancer in India was 67,795 in both sexes. The treatment of advanced Non-small cell lung cancer (NSCLC) saw a major paradigm shift with recent advances in molecular-targeted therapy. Immune checkpoint blockade therapy is one such novel strategy with promising clinical benefits in advanced NSCLC. Programmed cell death receptor-1/Programmed cell death ligand-1 (PD-1/PD-L1) pathway is one such checkpoint and has thus become the current area of interest in the treatment of lung carcinoma. The PD-1/ PD-L1 pathway is under active investigation as it represents a promising therapeutic target in NSCLC. The expression of PD-L1 in tumor cells has been suggested as a predictive marker of the clinical response to PD-Journal of Cancer Therapy tients of NSCLC. Among our study population, 40% of the patients exhibited PD-L1 immunopositivity (≥1%) with 28% of them having any expression (TPS 1% -49%) and 12% of them having a high expression (TPS ≥ 50%) of PD-L1. Majority of them exhibited adenocarcinoma type of NSCLC under which the solid subtype showed a direct correlation with PD-L1 positivity (p-value: 0.004) with a poorly differentiated tumor histology being common in our population in relation to PD-L1 positivity (p-value: 0.043). PD-L1 expression did not correlate with age, gender, smoking status or clinical stage in our study. No association was found between tumor histology (SCC or AC) and driver mutation status with expression of PD-L1 in the present study. Conclusions: In our study, PD-L1 immunopositivity was found in 40% of patients and majority of them exhibited adenocarcinoma type of NSCLC. There was no correlation of PD-L1 expresion with age, gender, clinical stage, smoking status and tumor histology.

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Unique distribution of programmed death ligand 1 (PD-L1) expression in East Asian non-small cell lung cancer

Cited by 54 publications

References 22 publications

Intratumoral heterogeneity in programmed death‐ligand 1 immunoreactivity is associated with variation in non‐small cell lung carcinoma histotype

Intratumoral heterogeneity in programmed death‐ligand 1 immunoreactivity is associated with variation in non‐small cell lung carcinoma histotype

Cytology cell blocks from malignant pleural effusion are good candidates for PD-L1 detection in advanced NSCLC compared with matched histology samples

Correlation of Programmed Death Ligand-1 (PD-L1) Expression with Clinicopathological Features in Non-Small Cell Lung Carcinoma: Experience from a Tertiary Cancer Care Center in India

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