Comparative analysis of programmed cell death ligand 1 assays in renal cell carcinoma

Lee, Kyu Sang; Choe, Gheeyoung; Yun, Sangchul; Lee, Kyoungyul; Moon, Seyoung; Lee, Sangchul; Hong, Sung Kyu; Byun, Seok Soo

doi:10.1111/his.14054

Cited by 5 publications

(3 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PD-L1 expression was first evaluated according to the intensity (negative, weak, moderate, or strong) and the percentage of positive tumor cells and immune cells, including lymphocytes and macrophages. Either tumor cells with membranous patterns or immune cells with cytoplasmic or membranous patterns showing more than weak intensity in > 1% were considered positive for PD-L1 expression [ 11 ]. The investigator was blinded to the associated clinicopathological information.…”

Section: Methodsmentioning

confidence: 99%

PD-L1 Upregulation by the mTOR Pathway in VEGFR-TKI–Resistant Metastatic Clear Cell Renal Cell Carcinoma

et al. 2023

View full text Add to dashboard Cite

Tyrosine kinase inhibitors (TKI) targeting vascular endothelial growth factor receptor (VEGFR) signaling pathways have been used for metastatic clear cell renal cell carcinoma (mCCRCC), but resistance to the drug develops in most patients. We aimed to explore the underlying mechanism of the TKI resistance with regard to programmed death-ligand 1 (PD-L1) and to investigate signaling pathway associated with the resistant mechanism. Materials and MethodsTo determine the mechanism of resistance, 10 mCCRCC patients from whom tumor tissues were harvested at both the pretreatment and the TKI-resistant post-treatment period were included as the discovery cohort, and their global gene expression profiles were compared. A TKI-resistant renal cancer cell line was established by long-term treatment with sunitinib. ResultsAmong differentially expressed genes in the discovery cohort, increased PD-L1 expression in post-treatment tissues was noted in four patients. Pathway analysis showed that PD-L1 expression was positively correlated with the mammalian target of rapamycin (mTOR) signaling pathway. The TKI-resistant renal cancer cells showed increased expression of PD-L1 and mTOR signaling proteins and demonstrated aggressive tumoral behaviour. Treatment with mTOR inhibitors down-regulated PD-L1 expression and suppressed aggressive tumoral behaviour, which was reversed with stimulation of the mTOR pathway. ConclusionThese results showed that PD-L1 expression may be increased in a subset of VEGFR-TKIresistant mCCRCC patients via the mTOR pathway.

show abstract

Section: Methodsmentioning

confidence: 99%

PD-L1 Upregulation by the mTOR Pathway in VEGFR-TKI–Resistant Metastatic Clear Cell Renal Cell Carcinoma

et al. 2023

View full text Add to dashboard Cite

show abstract

“…When these 3 tests were compared, PD-L1 expression scores showed moderate to high positive correlation. Staining in TIMCs was statistically similar, although relatively less frequent with E1L3N [29]. Sommer et al compared PD-L1 expression with 4 different immunohistochemical methods in advanced RCC and found that PD-L1 positivity in tumours with Ventana SP142 was significantly lower than the others (Ventana SP263, Dako 28-8, Dako 22C3).…”

Section: Ccrcc -Clear Cell Renal Cell Carcinoma Chrcc -Chromophobe Re...mentioning

confidence: 98%

Evaluation of pd-1, pd-l1, and cytotoxic T-lymphocyteassociated protein 4 expressions together with clinicopathological findings in clear cell, papillary, and chromophobe types of renal cell carcinoma

Inceman¹,

Toyran²,

Bayazıt³

et al. 2022

pjp

View full text Add to dashboard Cite

Our study aimed to determine the expressions of programmed death protein 1 (PD-1), programmed death ligand protein 1 (PD-L1), and cytotoxic T-lymphocyteassociated protein 4 (CTLA-4) to investigate and compare the differences between early and advanced cases in the 3 most common types of renal cell carcinoma (RCC) and reveal their correlations with prognosis and survival. A total of 166 RCC cases diagnosed between 2010 and 2019 in our hospital were included. PD-1, PD-L1, and CTLA-4 markers were applied to the paraffin blocks of the cases using an immunohistochemical method, and their expression status was evaluated by distinguishing subtypes in advanced-and early-stage RCCs. It was observed that PD-L1 positivity in the tumour cells, in clear cell RCC, was statistically significantly more frequent in advanced-stage cases compared to early-stage cases. It was concluded that cases with PD-L1 positivity in tumourinfiltrating mononuclear cells (TIMC) in clear cell and chromophobe RCC had a shorter survival. The frequency of perinephritic fat invasion and necrosis was higher in cases with PD-L1 expression in TIMC. We think that PD-1, PD-L1, and CTLA-4 must be considered together in advanced stage RCC for the treatment of both pathway inhibitors. Further large studies will shed light on the immunotherapy options at the advanced stage of all RCC types even in the absence of metastasis.

show abstract

“…Ma et al reported that E1L3N showed poor staining of gastric tumor cells compared to SP142 and 28-8 in surgical specimens on different detection platforms (13). Similarly, the E1L3N assay using Ventana BenchMark XT automated platform showed lower PD-L1 positivity of bile duct tumor cells than SP263 and 22C3 assays in tissue microarrays (TMA) or whole tissue sections (24). The PD-L1 expression status in NSCLC biopsy samples using 22C3 and E1L3N antibodies on the Dako AutostainerLink-48 platform remains only partially understood.…”

Section: Introductionmentioning

confidence: 99%

High concordance of programmed death-ligand 1 expression with immunohistochemistry detection between antibody clones 22C3 and E1L3N in non-small cell lung cancer biopsy samples

Zhang¹,

Cao²,

Gao³

et al. 2020

Transl Cancer Res TCR

View full text Add to dashboard Cite

Background: The detection of programmed death-ligand 1 (PD-L1) expression can enrich for patients who respond to anti-programmed cell death 1 (PD-1)/PD-L1 therapies. Though, for most laboratories, the cost of PD-L1 22C3 pharmDx is prohibitive for widespread use, whereas the laboratory-developed test (LDT) PD-L1 E1L3N antibody clone is widely available and inexpensive. This study aims to explore the analytical performance of E1L3N on the Dako Autostainer Link-48 platform and further evaluate the concordance of E1L3N and 22C3 expression in non-small cell lung cancer (NSCLC) biopsy samples.Methods: A total of 171 NSCLC biopsy samples were utilized in this study. Cases with less than 100 tumor cells were excluded. Serial sections of representative blocks were used for immunohistochemistry (IHC) staining. The staining protocol was performed according to the standard PD-L1 IHC 22C3 pharmDx package. PD-L1 staining on the tumor cell membrane was detected by immunofluorescence.Results: At a 1% cutoff value, PD-L1 was positive in 46.2% of patients using clone 22C3 and 42.1% of patients using E1L3N assays. At a 50% cutoff value, PD-L1 was positive in 16.4% of patients using clone 22C3 and 15.2% of the patients using E1L3N assays. Cohen's kappa was used to evaluate the concordance of the PD-L1 expression between clone 22C3 and E1L3N. The kappa values were 0.893 [95% confidence interval (CI): 0.826-1] at the 1% cutoff and 0.868 (95% CI: 0.764-1) at the 50% cutoff. An evaluation of the intraclass correlation coefficients (ICCs) between the antibodies was used to quantify the interassay variability for PD-L1 expression in tumor cells. ICCs showed high concordance between the two antibodies (0.955, 95% CI: 0.939-0.967). Cohen's kappa was also used to assess the consistency of the PD-L1 evaluation between two pathologists. The kappa values were 0.941 and 0.912 at the 1% cutoff, and 0.904 and 0.909 at the 50% cutoff for clone 22C3 and E1L3N expression, respectively. Conclusions:The results indicated that the clone E1L3N assay has a high concordance with 22C3. The PD-L1 clone E1L3N assay is reliable and cost-effective, and could be used as a primary screening agent for PD-L1 IHC staining in pathological laboratories, especially in a research setting.

show abstract

Comparative analysis of programmed cell death ligand 1 assays in renal cell carcinoma

Cited by 5 publications

References 33 publications

PD-L1 Upregulation by the mTOR Pathway in VEGFR-TKI–Resistant Metastatic Clear Cell Renal Cell Carcinoma

PD-L1 Upregulation by the mTOR Pathway in VEGFR-TKI–Resistant Metastatic Clear Cell Renal Cell Carcinoma

Evaluation of pd-1, pd-l1, and cytotoxic T-lymphocyteassociated protein 4 expressions together with clinicopathological findings in clear cell, papillary, and chromophobe types of renal cell carcinoma

High concordance of programmed death-ligand 1 expression with immunohistochemistry detection between antibody clones 22C3 and E1L3N in non-small cell lung cancer biopsy samples

Contact Info

Product

Resources

About