Programmed death–ligand 1 expression on direct Pap‐stained cytology smears from non–small cell lung cancer: Comparison with cell blocks and surgical resection specimens

Lozano, Marı́a D.; Abengozar-Muela, Marta; Echeveste, José; Súbtil, José Carlos; Bertó, Juan; Gúrpide, Alfonso; Calvo, Alfonso; Andrea, Carlos E. de

doi:10.1002/cncy.22155

Cited by 32 publications

(40 citation statements)

References 33 publications

(85 reference statements)

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“…Interestingly, 22 CBs have been included in the Blueprint (BP) PD‐L1 Immunohistochemistry Comparability Phase 2 Project, which aims to harmonize in real life practice the clinical use of different commercial PD‐L1 IHC assays on 81 routine lung cancer samples 5 . Noteworthy, several studies carried out on matched cytological and histological samples from the same patients have reported comparable results between CBs, surgical resections and small biopsy specimens in terms of adequacy rate, level of PD‐L1 expression, and clinical outcomes 6‐18 . Moreover, CBs also represent a valuable source of diagnostic material even in the early stages of the disease.…”

Section: Introductionmentioning

confidence: 99%

PD‐L1 expression in cell‐blocks of non‐small cell lung cancer: The impact of prolonged fixation

Vigliar

Iaccarino

Campione

et al. 2020

Diagnostic Cytopathology

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Introduction In the selection of non‐small cell lung cancer (NSCLC) patients for immunotherapy, specimen processed as cell blocks (CBs) may be the only available material to assess PD‐L1 expression. Therefore, optimal CB preparation becomes paramount. In this context, here we assessed whether inadequate fixation time might be one of the pre‐analytical factors affecting PD‐L1 expression. Methods Ex vivo CBs from placental (n = 3) and NSCLC (n = 8) resection specimens were obtained. PD‐L1 staining was performed on CBs prepared at increasing fixation times (12 hours, 48 hours, 72 hours, 96 hours, 168 hours and 504 hours) using the companion diagnostic SP263 Assay and a validated 22C3 laboratory developed test (LDT). Staining intensity and percentage of positive cells were evaluated. Results All placental CBs showed moderate to strong PD‐L1 positivity in most cells, regardless of the fixation time. Likewise, the percentage of SP263‐stained NSCLC cells was similar at all fixation times except for one case, which showed less intense SP263 staining at 168 hours. Conversely, in 5/8 cases, the 22C3 LDT percentage of positive cells and staining intensity decreased at 168 hours and 504 hours. Conclusions Our results show that fixation time influences the performance of 22C3 LDT on CBs. Thus, we recommend that the fixation time of cytological materials be carefully checked, especially when PD‐L1 testing is delayed until the oncology request. Indeed, delays in tissue processing and paraffin embedding may lead to sub‐optimal performance of PD‐L1 staining on CBs.

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Section: Introductionmentioning

confidence: 99%

PD‐L1 expression in cell‐blocks of non‐small cell lung cancer: The impact of prolonged fixation

Vigliar

Iaccarino

Campione

et al. 2020

Diagnostic Cytopathology

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“…The cytology-histology correlation at the ≥1% cutoff was found to be weak [13]. A similar study focused on smears as substrate was conducted by Lozano et al [20] who used mainly CBs as reference (12/62 patients with surgical specimens only) and reported high concordance. Torous et al [14] performed a bulk comparison with 94 CB and 138 surgical pathology specimens.…”

Section: Discussionmentioning

confidence: 99%

Implementation of PD-L1 22C3 IHC pharmDx<sup>TM</sup> in Cell Block Preparations of Lung Cancer: Concordance with Surgical Resections and Technical Validation of CytoLyt® Prefixation

Lou

Kinoshita

et al. 2020

Acta Cytologica

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Background: Programmed death ligand-1 (PD-L1) assessed by immunohistochemistry (IHC) is used as biomarker for pembrolizumab therapy in advanced stage lung cancer patients. However, data permitting direct performance comparison between cytology and surgical specimen types are limited since both specimens from a single tumor site are infrequently available. In addition, alcohol fixation used with cytology specimens requires technical validation of the PD-L1 IHC assay before clinical use. We here report our experience with implementation of the PD-L1 22C3 IHC pharmDxTM assay for cytologic samples at a large tertiary cancer center. Study Design: Archival formalin-fixed (FF), paraffin-embedded cell blocks (CBs) and subsequent lung tumor resections (LTRs) from the same anatomical site were used for a direct comparison of PD-L1 tumor proportion scores (TPSs). TPS values were independently determined by one surgical lung pathologist and two cytopathologists blinded to the specimen pairs. An interim analysis was performed to facilitate the pooling of expertise among observers. After PD-L1 22C3 IHC pharmDxTM implementation for FF cytology specimens, dual-processed samples were used for a prospective technical validation of CytoLyt® prefixation (CF). Digital image analysis was performed for a subset of dual-processed specimens. Results: Eighty-one CBs and LTRs were included for comparison of the specimen types. PD-L1 assessment in CBs had an accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 88.9/72.8, 66.7/73.5, 95.2/72.3, 80.0/65.8, and 90.9/79.1% for the ≥50/≥1% cutoff, respectively. The intraclass correlation coefficient was 0.84 (95% confidence interval [CI]: 0.76, 0.90), and it improved after interim analysis (before: 0.79 and after: 0.92). The overall concordance between CF and FF for the categories defined by the ≥50/≥1% cutoff values was 90.4% (95% CI: 79.0, 96.8). Similar assay performance was confirmed by digital analysis. Conclusions: PD-L1 22C3 IHC pharmDxTM shows good reliability if used with CB preparations. CF does not impact assay results significantly. Clinical validation with outcome data is needed, and digital methods of assessment should be further investigated.

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“…Lozano et al studied PD‐L1 expression on Papanicolaou‐stained cytological smears and compared with formalin‐fixed paraffin‐embedded samples (cytological cell blocks and surgical resection specimens) in 57 set of samples using 2 IHC 22C3 pharmDx assay and the Ventana SP263 Assay. They noted a concordance rate of 92.7% between the two assays on cytological specimens 27 . Fujimoto et al 28 concluded in their comparative studies that SP263 assay can be used in the place of the 22C3 assay for assessing PD‐L1 expression.…”

Section: Discussionmentioning

confidence: 99%

Performance of Ventana SP263 PD‐L1 assay in endobronchial ultrasound guided‐fine‐needle aspiration derived non‐small‐cell lung carcinoma samples

Chauhan

Siegel

Freese

et al. 2020

Diagnostic Cytopathology

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Background Introduction of programmed death‐ligand 1 (PD‐L1) inhibitors has significantly changed the treatment landscape of non‐small‐cell lung carcinomas (NSCLC). Since endobronchial ultrasound guided fine‐needle aspiration (EBUS FNA) has become the primary diagnostic and staging modality for NSCLC, this study was pursued to determine the adequacy of Ventana SP263 PD‐L1 assay in cytology cell blocks. Design Fifty NSCLC cases with cytology and corresponding histology specimens obtained between 2014 and 2018 were identified. After assessing for adequacy (100 or more tumor cells), forty cases were selected for Ventana SP263 PD‐L1 immunohistochemistry (IHC) assay and assessed for tumor proportion scores (TPS) and staining intensity scores (SIS) and analyzed for concordance. Results Of the 40 matched pairs 33 (82.5%) showed concordant PD‐L1 expression. On cytology, 32 cases were positive (8 high‐expressors and 24 low‐expressors) of which 27 were concordant and 5 discordant with matched histology specimens. On histology, 29 cases were positive (7 high‐expressor and 22 low‐expressors) while 11 cases were negative for PD‐L1 expression of which 6 had concordant negative cytology. The intraclass correlation coefficients (ICC) for TPS was 0.81 with 95% confidence interval (0.68, 0.9) and for the SIS, it was 0.78 with 95% CI (0.62, 0.88), both considered as having excellent agreement. Conclusion With an overall concordance rate of 82.5% between cytology and histology specimen, this study demonstrates the feasibility of PD‐L1 IHC with SP263 clone on cytology samples of NSCLC and adds to a growing body of evidence validating the use of cytology cell blocks for PD‐L1 expression testing.

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Programmed death–ligand 1 expression on direct Pap‐stained cytology smears from non–small cell lung cancer: Comparison with cell blocks and surgical resection specimens

Cited by 32 publications

References 33 publications

PD‐L1 expression in cell‐blocks of non‐small cell lung cancer: The impact of prolonged fixation

PD‐L1 expression in cell‐blocks of non‐small cell lung cancer: The impact of prolonged fixation

Implementation of PD-L1 22C3 IHC pharmDx<sup>TM</sup> in Cell Block Preparations of Lung Cancer: Concordance with Surgical Resections and Technical Validation of CytoLyt® Prefixation

Performance of Ventana SP263 PD‐L1 assay in endobronchial ultrasound guided‐fine‐needle aspiration derived non‐small‐cell lung carcinoma samples

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