Validation of the immunohistochemical expression of programmed death ligand 1 (PD-L1) on cytological smears in advanced non small cell lung cancer

•Currently, only FFPE samples are acceptable for the IHC assessment of PD-L1 in NSCLC.•Cytological smears are the only available material for a subset of patients.•IHC for PD-L1 in cytological smears of NSCLC is feasible using the >50% cut-off.•PD-L1 IHC on cytological smears expands the pool of...

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Published in:Lung cancer (Amsterdam, Netherlands) Vol. 126; pp. 9 - 14
Main Authors: Capizzi, Elisa, Ricci, Costantino, Giunchi, Francesca, Zagnoni, Stefano, Ceccarelli, Claudio, Gómez, Begoña Urrios Álvarez, Casolari, Laura, Gelsomino, Francesco, Trisolini, Rocco, Fiorentino, Michelangelo, Ardizzoni, Andrea
Format: Journal Article
Language:English
Published: Ireland Elsevier B.V 01.12.2018
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ISSN:0169-5002, 1872-8332, 1872-8332
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Summary:•Currently, only FFPE samples are acceptable for the IHC assessment of PD-L1 in NSCLC.•Cytological smears are the only available material for a subset of patients.•IHC for PD-L1 in cytological smears of NSCLC is feasible using the >50% cut-off.•PD-L1 IHC on cytological smears expands the pool of NSCLC candidate to immunotherapy. Introduction The assessment of PD-L1 expression by immunohistochemistry is mandatory for the administration as first-line therapy of the anti PD-1 check-point inhibitor Pembrolizumab in patients with advanced non-small-cell lung cancer (NSCLC). Currently, only formalin-fixed paraffin-embedded samples are acceptable for PD-L1 immunostaining with the anti-PD-L1 antibodies 22-C3 and SP263. We investigated retrospectively the accuracy of the anti PD-L1 antibodies 22-C3, 28-28, SP263 in 50 paired histological samples and cytological smears of NSCLC patients. Results The accuracy of the three antibodies for the detection of PD-L1 in histological samples was higher for the antibody SP263 (AUC/ROC = 1) compared to the clones 28-8 (AUC/ROC =,991) and 22-C3 (AUC/ROC =,942). The overall concordance between histological samples and cytological smears using the SP263 clone was moderate (kappa = 0,364). However when the cyto-histological concordance was calculated using just the <50% vs ≥50% cut-off the agreement (kappa = 0.626) was good. The accuracy of the antibody SP263 in cytological smears was good (AUC/ROC =,921). A fluorescent in situ hybridization analysis on 10 histological cases positive for PD-L1 at immunohistochemistry showed amplification of the CD274 gene only in one case. Conclusions Immunocytochemical staining for PD-L1 in diagnostic cytological smears of NSCLC is feasible and applicable at least using the >50% cancer cell cut-off. The three antibodies SP263, 22-C3 and 28-8 are all suitable for the diagnostic detection of PD-L1 on tissue sections with a superiority of the SP263 clone. The implementation of PD-L1 immunocytochemistry on cytological smears will likely expand the pool of NSCLC patients candidate to first-line immunotherapy.
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ISSN:0169-5002
1872-8332
1872-8332
DOI:10.1016/j.lungcan.2018.10.017