Programmed death‐ligand 1 immunoexpression in matched biopsy and liquid‐based cytology samples of advanced stage non‐small cell lung carcinomas

Jain, Deepali; Sukumar, Supraja; Mohan, Anant; Iyer, Venkateswaran K.

doi:10.1111/cyt.12605

Cited by 39 publications

(44 citation statements)

References 34 publications

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“…Herein, we found that cytology CB sections showed a strong positive correlation with resection specimens of the same anatomic site for PD-L1 assessment using the SP263 IHC assay. Taken together with our findings and a few studies of PD-L1 concordance between cytology and histology, [26][27][28][29][30][31] lung cancer patients with positive PD-L1 expression in the preoperative or diagnostic cytology do not need to repeat the test using the surgical resection specimens, at least using the cut-off of 1%. We propose that CBs are suitable materials for evaluating PD-L1 expression when simultaneously performing both diagnostic and molecular tests.…”

Section: Con Clus Ionsupporting

confidence: 79%

“…Second, recent studies reported cytology‐histology correlation in lung cancer, but we have doubts about the rigorous control of heterogeneity in tumours . These studies were done using samples collected by various methods.…”

Section: Discussionmentioning

confidence: 99%

“…[21][22][23][24][25][26] Second, recent studies reported cytology-histology correlation in lung cancer, but we have doubts about the rigorous control of heterogeneity in tumours. [25][26][27][28][29][30][31] These studies were done using samples collected by various methods. Cytology specimens were collected by fine needle aspiration, bronchial washing and bronchial brushing.…”

Section: Comparison Of Pd-l1 Expressionmentioning

confidence: 99%

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Cell‐blocks are suitable material for programmed cell death ligand‐1 immunohistochemistry: Comparison of cell‐blocks and matched surgical resection specimens in lung cancer

Pak

Roh

2019

Cytopathology

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Objective Programmed cell death ligand‐1 (PD‐L1) has emerged as a predictive biomarker in lung cancer. PD‐L1 immunohistochemistry (IHC) assay predicts the response to immunotherapy, but cytology specimens are often the only samples available in a considerable proportion of advanced lung cancer patients. We delineate practical feasibility and efficacy of cytology cell‐block (CB) specimens for PD‐L1 expression and concordance between cytology CBs and surgical resection specimens. Methods In total, 58 eligible patients with primary lung cancer who received computed tomography‐guided percutaneous needle aspiration and surgery were included. PD‐L1 IHC (clone SP263) was performed on CBs prepared from residual liquid‐based cytology material and matched surgical resection specimens. PD‐L1 positive tumour cell proportion was categorised in four score groups: (a) <1%; (b) ≤1% to <10%; (c) ≤10% to <50%, (d) ≥50%. Results Comparison of PD‐L1 expression in cytology CBs and matched surgical resection specimens showed a high concordance (κ value 0.65). According to the therapeutic guideline of immunotherapeutic agents, a positive percent agreement was 94.34%, and a negative percent agreement was 100% at a cut‐off value for positivity of 1% PD‐L1 expression. There was a significant difference observed with regard to rates of PD‐L1 positivity when comparing smoking history (P = 0.02), age (P = 0.04) and pathological TNM stage (P = 0.04). Conclusions The results show that cytology CBs evaluated for PD‐L1 IHC assay have high concordance with matched surgical resection specimens and can be used for assessing PD‐L1 expression. Also, we propose that CBs are suitable materials for evaluating PD‐L1 expression while simultaneously performing both diagnostic and molecular tests.

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Section: Con Clus Ionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Comparison Of Pd-l1 Expressionmentioning

confidence: 99%

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Cell‐blocks are suitable material for programmed cell death ligand‐1 immunohistochemistry: Comparison of cell‐blocks and matched surgical resection specimens in lung cancer

Pak

Roh

2019

Cytopathology

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“…In this study we have demonstrated substantial agreement between or liquid-based cytology slides appears less concordant with subsequent biopsy specimens. 15,[19][20][21] Bulk comparisons (ie, non-paired samples) appear to show slightly higher PD-L1 expression in cytology specimens, of uncertain significance. 22,23 PD-L1 IHC on histology specimens is acknowledged to be an imperfect biomarker and ultimately the ability of a test to predict responses to anti-PD-1 immunotherapy is the most appropriate standard against which to compare new tests or test conditions.…”

Section: Discussionmentioning

confidence: 97%

“…A number of previous studies have investigated the potential usefulness of cytology specimens in PD‐L1 IHC assessment in NSCLC, reviewed in Hernandez et al; however, the range of different assays, staining platforms, scoring systems and reported statistics makes comparison across studies difficult. In general, studies of paired histology and cell‐block specimens have shown acceptable concordance, while direct IHC performed on smears or liquid‐based cytology slides appears less concordant with subsequent biopsy specimens . Bulk comparisons (ie, non‐paired samples) appear to show slightly higher PD‐L1 expression in cytology specimens, of uncertain significance …”

Section: Discussionmentioning

confidence: 99%

Adequate tumour cellularity is essential for accurate PD‐L1 immunohistochemistry assessment on cytology cell‐block specimens

et al. 2020

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Objectives PD‐L1 immunohistochemistry (IHC) is an essential predictive biomarker for patients with non‐small cell lung cancer (NSCLC), required to inform treatment decisions regarding anti‐PD‐1 immune checkpoint inhibitor therapy. This study aims to investigate the concordance between PD‐L1 IHC assessed on NSCLC cytology and histology specimens and to determine the impactce of tumour cellularity. Methods Matched cytology and histology NSCLC specimens were retrieved from the archives of the Royal Melbourne Hospital and the Royal Prince Alfred Hospital. PD‐L1 IHC was performed concurrently on both specimens at the Peter MacCallum Cancer Centre using the SP263 assay kit on the Ventana Benchmark Ultra staining platform and scored by two experienced pathologists. Results Overall agreement between matched cytology and histology specimens was good (intraclass correlation coefficient = 0.653, n = 58); however, markedly increased when the analysis was limited to cell‐blocks with >100 tumour cells (intraclass correlation coefficient = 0.957, n = 29). Specificity at both 1% and 50% cut‐offs was high regardless of cellularity; however, sensitivity decreased in samples with <100 tumour cells. Conclusions PD‐L1 IHC on cytology cell‐block specimens in NSCLC is an acceptable alternative to histological specimens, provided adequate tumour cells are present. Clinicians and pathologists should be mindful of the risk of false negative PD‐L1 IHC in samples with low tumour cellularity, to avoid excluding patients from potentially beneficial treatment.

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Multiplex immune protein profiling of fine‐needle aspirates from patients with non‐small‐cell lung cancer reveals signatures associated with PD‐L1 expression and tumor stage

et al. 2021

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Biomarker signatures identified through minimally invasive procedures already at diagnosis of non-small-cell lung cancer (NSCLC) could help to guide treatment with immune checkpoint inhibitors (ICI). Here, we performed multiplex profiling of immune-related proteins in fine-needle aspirate (FNA) samples of thoracic lesions from patients with NSCLC to assess PD-L1 expression and identify related protein signatures. Transthoracic FNA samples from 14 patients were subjected to multiplex antibody-based profiling by proximity extension assay (PEA). PEA profiling employed protein panels relevant to immune and tumor signaling and was followed by Qlucore Ò Omics Explorer analysis. All lesions analyzed were NSCLC adenocarcinomas, and PEA profiles could be used to monitor 163 proteins in all but one sample. Multiple key immune signaling components (including CD73, granzyme A, and chemokines CCL3 and CCL23) were identified and expression of several of these proteins (e.g., CCL3 and CCL23) correlated to PD-L1 expression. We also found EphA2, a marker previously linked to inferior NSCLC prognosis, to correlate to PD-L1 expression. Our identified protein signatures related to stage included, among others, CXCL10 and IL12RB1. We conclude that transthoracic FNA allows for extensive immune and tumor protein profiling with assessment of putative biomarkers of important for ICI treatment selection in NSCLC.

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Programmed death‐ligand 1 immunoexpression in matched biopsy and liquid‐based cytology samples of advanced stage non‐small cell lung carcinomas

Cited by 39 publications

References 34 publications

Cell‐blocks are suitable material for programmed cell death ligand‐1 immunohistochemistry: Comparison of cell‐blocks and matched surgical resection specimens in lung cancer

Cell‐blocks are suitable material for programmed cell death ligand‐1 immunohistochemistry: Comparison of cell‐blocks and matched surgical resection specimens in lung cancer

Adequate tumour cellularity is essential for accurate PD‐L1 immunohistochemistry assessment on cytology cell‐block specimens

Multiplex immune protein profiling of fine‐needle aspirates from patients with non‐small‐cell lung cancer reveals signatures associated with PD‐L1 expression and tumor stage

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