Concordance of <scp>PD</scp>‐L1 expression in matched urothelial bladder cancer specimens

Jong, Joep J. de; Stoop, Hans; Nieboer, Daan; Boormans, Joost L.; Leenders, Geert J.L.H. van

doi:10.1111/his.13710

Cited by 31 publications

(20 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Numerous studies confirm the efficacy of inhibitors of control points in cancer immunotherapy [20][21][22][23][24][25][26]. However, not all patients respond to anti-PD-L1 therapy to the same extent which highlights the need to search for novel biomarkers to further stratify the treatment groups [27,28].…”

Section: Discussionmentioning

confidence: 99%

The type of distribution of PD-L1 positive immune cells and PD-L1 expression in tumor cells correlate with the development of non-classical differentiation in urinary bladder cancer

Matusiak¹,

Starzyński²,

Jóźwicki

et al. 2019

Medical Research Journal

View full text Add to dashboard Cite

Background: The basic diagnostic tool of urinary bladder cancer is the histopathological assessment. However, it is insufficient to accurately predict the progression of this disease. There is a need to look for new prognostic factors that will make the therapeutic process more effective. The aim of this study is to evaluate the effect of activation of a PD1-PD-L1 immune checkpoint in immune effector cells (IECs) and tumor cells, on the development of malignancy in the form of non-classic differentiation in urinary bladder cancer. Materials and methods: 110 patients with stage pT1-pT4 urothelial bladder carcinoma who underwent radical cystectomy/cystoprostatectomy between 2011 and 2014 were included in the study. Tumor advancement (pT stage), grade (G), as well as, non-classic differentiation frequency and number were evaluated pathologically. In each case, the area of the tumor containing PD-L1+ IECs was analyzed. The distribution of PD-L1+ immune effector cells within the tumor was also assessed as dispersed or aggregated. Results: The frequency of non-classic differentiation was significantly lower in urothelial bladder cancer tumors with a dispersed pattern of distribution of PD-L1+ IECs. A correlation between the extent of PD-L1 expression in tumor cells and the non-classic differentiation number in UBC was identified. Conclusions: The distribution of cells expressing the immune checkpoint biomarker PD-L1 constitutes a new prognostic factor and may play a key role in the selection of individualized immunotherapy. In addition, the evaluation of non-classic differentiation in the tumor may complement the assessment of PD-L1 expression due to its capacity to characterize the current malignant potential of the tumor, whereas the assessment of extent and distribution of PD-L1+ in tumor-associated immune cells indicates the functional status of the immune system.

show abstract

Section: Discussionmentioning

confidence: 99%

The type of distribution of PD-L1 positive immune cells and PD-L1 expression in tumor cells correlate with the development of non-classical differentiation in urinary bladder cancer

Matusiak¹,

Starzyński²,

Jóźwicki

et al. 2019

Medical Research Journal

View full text Add to dashboard Cite

show abstract

“…The use of patient material for scientific purposes was approved by the local Medical Research Ethics Committee (Rotterdam, Netherlands, MEC-2014-553). All haematoxylin and eosin (HE) slides were reviewed by a genitourinary pathologist (GvL), who monitored the following: grade (WHO1973 and 2016), pT stage (TNM 8th edition), surgical margin status, presence of carcinoma in situ (CIS), vascular invasion (VI), and presence of variant histology (squamous, glandular, neuroendocrine, sarcomatoid) [12]. In the present study, whole tissue slides were newly stained with the PD-L1 SP263 assay and compared to PD-L1 SP142 stainings, which had been performed on the same slides and published previously [12].…”

Section: Patient Selection and Pathological Reviewmentioning

confidence: 99%

“…However, little is known about the variability of PD-L1 expression among different tumour tissues from individual patients [10,11]. Previously, we found poor concordance of PD-L1 expression in urothelial cancer as determined in matched transurethral resection of the bladder tumour (TURBT), RC, and lymph node metastasis (LN) using the VENTANA PD-L1 (SP142) assay [12]. The PD-L1 (SP142) assay has been used as companion diagnostic for atezolizumab and is based on PD-L1 expression on tumour-associated immune cells (IC) only.…”

Section: Introductionmentioning

confidence: 96%

“…The VENTANA PD-L1 (SP263) assay, which is used as companion diagnostic for durvalumab, takes into account PD-L1 expression on both TC and IC, and has, like the SP142 assay, been developed for a VENTANA BenchMark ULTRA platform. The objective of this study was to determine the concordance of PD-L1 expression using the SP263 assay in matched TURBT, RC, and LN samples, and to compare its outcome with the SP142 assay, which had been performed previously on the same population [12].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

Urothelial 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.

show abstract

“…The results of clinical trials have demonstrated a significant correlation between PD-L1 expression in some tumors and the effectiveness of treatment using immune checkpoint inhibitors (ICI) [14][15][16][17][18][19], especially in early stages of the disease [20], and in combination therapies [21]. However, some patients who meet the criteria for therapy do not respond well to anti-PD-L1 treatment [22,23]. Thus, finding new eligibility criteria for immunotherapy to increase its efficacy and safety is paramount.…”

Section: Introductionmentioning

confidence: 99%

Expression of PD-L1 in tumor and immune system cells affects the survival of patients with urinary bladder cancer

Matusiak¹,

Dzierżawski²,

Jóźwicki³

et al. 2019

Medical Research Journal

View full text Add to dashboard Cite

Background: The prediction of tumor malignancy is still one of the most demanding diagnostic tasks in urinary bladder cancer because of its clinicopathological heterogeneity. The aim of this study was to evaluate the expression of PD-L1 in tumor cells (TCs) and immune effector cells (IECs) as well as the pattern of distribution of PD-L1+ IECs within the tumor (dispersed or aggregated) and their association with survival of patients with pT1-pT4 urinary bladder cancer. Materials and methods: 110 patients with stage pT1-pT4 urothelial bladder carcinoma who underwent radical cystectomy/cystoprostatectomy between 2011 and 2014 were included in the study. Paraffin blocks most representative of the tumor were selected for H&E staining as well as immunostaining with the use of rabbit anti-PD-L1 (Ventana clone SP142, Roche). In each sample, the area of the tumor containing PD-L1+ IECs, as well as, the pattern of distribution (dispersed or aggregated) of PD-L1+ immune effector cells within the tumor were analyzed. In addition, the expression of PD-L1 in TCs was also assessed. Results: Patients had a shorter survival time in pT2-pT4 cases without TCs expressing PD-L1 (p = 0.007) and/or when PD-L1+ IECs displayed a predominantly dispersed pattern of distribution (p = 0.013). Conclusions: The expression of PD-L1 on TCs and IECs is a prognostic factor which allows for stratification of patient survival in UBC. The predominance of dispersed or aggregated pattern of distribution of PD-L1+ IECs in the tumor may be considered as a new prognostic factor in pT1-T4 UBC and indicate the functional status of the immune system.

show abstract

Concordance of PD‐L1 expression in matched urothelial bladder cancer specimens

Cited by 31 publications

References 13 publications

The type of distribution of PD-L1 positive immune cells and PD-L1 expression in tumor cells correlate with the development of non-classical differentiation in urinary bladder cancer

The type of distribution of PD-L1 positive immune cells and PD-L1 expression in tumor cells correlate with the development of non-classical differentiation in urinary bladder cancer

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

Expression of PD-L1 in tumor and immune system cells affects the survival of patients with urinary bladder cancer

Contact Info

Product

Resources

About