Comparison of 22C3 PD-L1 Expression between Surgically Resected Specimens and Paired Tissue Microarrays in Non–Small Cell Lung Cancer

Li, Chao; Huang, Cheng; Mok, Tony; Zhuang, W.; Xu, Haipeng; Qin, Miao; Fan, Xirong; Zhu, Weixing; Huang, Yun-jian; Lin, Xiandong; Jiang, Kan; Hu, Dan; Chen, Xiaohui; Huang, Peisha; Lin, Gen

doi:10.1016/j.jtho.2017.07.015

Cited by 54 publications

(41 citation statements)

References 30 publications

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“…In relation to general positivity at cutoffs of 1% and 50%, the results reported by Li et al 20 are similar to ours even though two different clones were used (22C3 by Li et al and SP263 by us).…”

Section: Discussionsupporting

confidence: 86%

“…At a cutoff of 1% these authors found 37% of cases to be positive, with a discordance rate of 13.2%, whereas at a cutoff of 50% positivity was found in 11% of cases, with a discordance rate of 6.8%. 20 Notably, these authors built their TMA by using single cores with a diameter of 2 mm for each case; instead, we used multiple smaller cylinders (1 mm) to have a more comprehensive picture for each case and to allow better computation thanks to a higher number of cores. In addition, even with consideration of our results on only a single core (and even though the core was smaller), our data are in line with those of these authors in terms of discordance rates (13% and 4.2% for cutoffs of 1% and 50%, respectively).…”

Section: Discussionmentioning

confidence: 99%

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PD-L1 Expression Heterogeneity in Non–Small Cell Lung Cancer: Defining Criteria for Harmonization between Biopsy Specimens and Whole Sections

Munari

Zamboni

Lunardi

et al. 2018

Journal of Thoracic Oncology

136

128

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

PD-L1 Expression Heterogeneity in Non–Small Cell Lung Cancer: Defining Criteria for Harmonization between Biopsy Specimens and Whole Sections

Munari

Zamboni

Lunardi

et al. 2018

Journal of Thoracic Oncology

136

128

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“…23 The difference between ELISA and IHC could also be explained by the fact that plasma reflects the entire tumour heterogeneity, whereas PD-L1 expression can be heterogeneous within one tumour site, but also between different tumour sites. [8][9][10][11][12][13][14] Finally, sPD-L1 could also be secreted by cells other than tumour cells, such as immune cells. Interestingly, we confirmed the variation of sPD-L1 concentrations by RT-PCR from circulating RNA in patients with the largest variations of sPD-L1 concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, IHC was performed on the diagnostic tumour specimens whereas PD-L1 expression varies with time and especially after CT. 6,7 Moreover, PD-L1 IHC interpretation can be difficult, as there is a spatial heterogeneity of PD-L1 expression, within one same tumour region or between two different tumour regions (primary and metastatic). [8][9][10][11][12][13][14] There is therefore an unmet need for developing new biomarkers to predict nivolumab efficacy. Tumour mutation load or IFN-g signature have recently been evaluated, 15,16 but their use in clinical practice is still challenging.…”

Section: Introductionmentioning

confidence: 99%

Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab

et al. 2018

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Immune checkpoint inhibitors, as nivolumab, are used in advanced non-small cell lung cancer (NSCLC). However, no associated biomarker is validated in clinical practice with this drug. We investigated herein immune-related blood markers in patients with advanced NSCLC treated with nivolumab. Plasma of 43 consecutive patients were prospectively collected at time of the diagnosis of cancer, at the initiation of nivolumab and at the first tumour evaluation (2 months). Concentrations of PD-L1 (sPD-L1), soluble PD-L2 (sPD-L2), Interleukine-2 (sIl-2), Interferon-gamma (sIFN-γ), and Granzyme B (sGranB) were quantified by ELISA. Cell free RNA was quantified by Reverse Transcriptase -PCR), and plasmatic microRNAs (miRNAs) were evaluated by targeted sequencing. Expression of PD-L1 on tumour biopsies was performed by immunohistochemistry using E13LN. High sPD-L1 at 2 months and increase of sPD-L1 concentrations were associated with poor response and absence of clinical benefit (nivolumab treatment less than 6 months). The variation of sPD-L1 concentrations were confirmed by RNA quantification. sPD-L1 concentrations were not correlated with PD-L1 expression on corresponding tumour samples. Low sGranB at nivolumab initiation was also associated with poor response. High sPD-L1 and low sGranB were associated with poor progression-free survival (PFS) and overall survival (OS). Low sPD-L2, low sIl-2 and high sIFN-γ were associated with grade 3-4 toxicities. Finally, miRNA screening showed that patients with clinical benefit (n = 9) had down-expression of miRNA-320b and -375 compared to patients with early progression at 2 months (n = 9). In conclusion, our results highlight the interest of circulating biomarkers in patients treated with nivolumab.

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“…As a result, it was found that CB representing the tumor and limited tissue samples give correct and reliable results in the assessment of PD-L1 expression. Moreover, there are also studies comparing the expression value in tumor cells in biopsy and resection samples (12,13). In fact, the presence of immune reaction varying across regions in tumors is a known fact (14).…”

Section: Resultsmentioning

confidence: 99%

Programmed Death-ligand 1 Expression Analysis for Non-small Cell Lung Cancer in Tissues Sampled Using Different Methods

Ürer¹,

Günlüoğlu²,

Cansever³

et al. 2020

Haseki

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This study aims at investigating the concordance of programmed death-ligand 1 (PD-L1) expression in non-small cell cancer tissues that have been sampled using different methods and its relationship with the pathologic parameters of tumors. Methods: PD-L1 expression assays were made on the cell blocks taken using fine needle aspiration, the small tissue samples representing endoscopic biopsy and the large tissue samples representing the resected tumor taken from the tumors of 100 subjects diagnosed with non-small cell lung cancer; their percentage values were evaluated and their groups were determined based on these values. Results: The average difference in expression rates found through different sampling methods was close to 0, and the values of such differences changed mostly in a narrow range. In paired comparisons, a good level of concordance was observed between all the sampling methods. The values were 0.8865 (SE: 0.0306, CI: 0.8264-0.9466) in the comparison of tumor tissue (TT) and small biopsy (SB): 0.8637, (SE: 0.033, CI: 0.7989-0.9285) TT to cell block (CB): 0.8916, (SE: 0.0272, CI: 0.8383-0.9449) SB tissue to the CB. Conclusion: Therefore, it can be concluded that the PD-L1 expression does not differ between the tissues sampled through various methods in non-small cell lung cancers.

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Comparison of 22C3 PD-L1 Expression between Surgically Resected Specimens and Paired Tissue Microarrays in Non–Small Cell Lung Cancer

Cited by 54 publications

References 30 publications

PD-L1 Expression Heterogeneity in Non–Small Cell Lung Cancer: Defining Criteria for Harmonization between Biopsy Specimens and Whole Sections

PD-L1 Expression Heterogeneity in Non–Small Cell Lung Cancer: Defining Criteria for Harmonization between Biopsy Specimens and Whole Sections

Predictive role of plasmatic biomarkers in advanced non-small cell lung cancer treated by nivolumab

Programmed Death-ligand 1 Expression Analysis for Non-small Cell Lung Cancer in Tissues Sampled Using Different Methods

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