ArticleCancer cytopathology2021
Formalin fixation for optimal concordance of programmed death-ligand 1 immunostaining between cytologic and histologic specimens from patients with non-small cell lung cancer.
Article in Cancer cytopathology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
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Who cites it
12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- Why PD-L1 expression varies between studies of lung cancer: results from a Bayesian meta-analysis.Scientific reports · 2025Pooled it
- Program death ligand-1 immunocytochemistry in lung cancer cytological samples: A systematic review.Diagnostic cytopathology · 2022Pooled it
- High accuracy in detecting HER2-low status in FNA of primary and metastatic breast cancer.Cancer cytopathology · 2026Article
- Development of a Novel Peptide with RGD Tumor Homing Motif: Evaluation of its Anticancer Potential in Hepatocellular Carcinoma and Colon Cancer Cells.Recent patents on biotechnology · 2025Article
- Diagnostic and Predictive Immunocytochemistry in Lung Cancer.Acta cytologica · 2025Review
- Evaluation of a Novel Fixative Solution for Liquid-Based Cytology in Diagnostic Cytopathology.Diagnostics (Basel, Switzerland) · 2023Article
- Assessing PD-L1 Expression in Head and Neck Squamous Cell Carcinoma: Trials and Tribulations.Head and neck pathology · 2023Review
- Comparative evaluation of PD-L1 expression in cytology imprints, circulating tumour cells and tumour tissue in non-small cell lung cancer patients.Molecular oncology · 2023Article
- Nationwide differences in cytology fixation and processing methods and their impact on interlaboratory variation in PD-L1 positivity.Virchows Archiv : an international journal of pathology · 2023Article
- PD-L1 Expression in Non-Small Cell Lung Cancer: Data from a Referral Center in Spain.Diagnostics (Basel, Switzerland) · 2021Article
- Formalin fixation for optimal concordance of programmed death-ligand 1 immunostaining between cytologic and histologic specimens from patients with non-small cell lung cancer.Cancer cytopathology · 2021Article
- PD-L1 Testing in Cytological Non-Small Cell Lung Cancer Specimens: A Comparison with Biopsies and Review of the Literature.Acta cytologica · 2021Review
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmunohistochemical staining of programmed death-ligand 1 (PD-L1) is used to determine which patients with non-small cell lung cancer (NSCLC) may benefit most from immunotherapy. Therapeutic management of many patients with NSCLC is based on cytology instead of histology. In this study, concordance of PD-L1 immunostaining between cytology cell blocks and their histologic counterparts was analyzed. Furthermore, the effect of various fixatives and fixation times on PD-L1 immunoreactivity was studied.
methodsPaired histologic and cytologic samples from 67 patients with NSCLC were collected by performing fine-needle aspiration on pneumonectomy/lobectomy specimens. Formalin-fixed, agar-based or CytoLyt/PreservCyt-fixed Cellient cell blocks were prepared. Sections from cell blocks and tissue blocks were stained with SP263 (standardized assay) and 22C3 (laboratory-developed test) antibodies. PD-L1 scores were compared between histology and cytology. In addition, immunostaining was compared between PD-L1-expressing human cell lines fixed in various fixatives at increasing increments in fixation duration.
resultsAgar cell blocks and tissue blocks showed substantial agreement (κ = 0.70 and κ = 0.67, respectively), whereas fair-to-moderate agreement was found between Cellient cell blocks and histology (κ = 0.28 and κ = 0.49, respectively). Cell lines fixed in various alcohol-based fixatives showed less PD-L1 immunoreactivity compared with those fixed in formalin. In contrast to SP263, additional formalin fixation after alcohol fixation resulted in preserved staining intensity using the 22C3 laboratory-developed test and the 22C3 pharmDx assay.
conclusionsPerforming PD-L1 staining on cytologic specimens fixed in alcohol-based fixatives could result in false-negative immunostaining results, whereas fixation in formalin leads to higher and more histology-concordant PD-L1 immunostaining. The deleterious effect of alcohol fixation could be reversed to some degree by postfixation in formalin.
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