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Assessment of programmed cell death ligand-1 expression by 4 diagnostic assays and its clinicopathological correlation in a large cohort of surgical resected non-small cell lung carcinoma

Modern Pathologyvolume 31pages13811390 (2018) | Download Citation


Immune checkpoint blockade targeting the PD-1/PD-L1 axis has recently demonstrated efficacy and promise in cancer treatment. Appropriate biomarker selection is therefore essential for improving treatment efficacy. However, the establishment of PD-L1 assay in pathology laboratories is complicated by the presence of multiple testing platforms using different scoring systems. Here we assessed the PD-L1 expression in 713 consecutive non-small cell lung carcinomas by four commercially available PD-L1 immunohistochemical assays, namely, 22C3, 28-8, SP142 and SP263. The analytical performances of the four assays and diagnostic performances across clinically relevant cutoffs were evaluated. The prevalence of PD-L1 (22C3) expression was 21% with a ≥50% cutoff and 56% with a ≥1% cutoff. High PD-L1 expression (using a ≥50% cutoff) was significantly associated with male sex (P = 0.001), ever smoking history (P < 0.001), squamous cell carcinoma (P = 0.001), large cell carcinoma (P < 0.001), lymphoepithelioma-like carcinoma (P = 0.006), sarcomatoid carcinoma (P < 0.001), mutant KRAS (P = 0.005) and wild-type EGFR (P = 0.003). Elevated PD-L1 expression was also significantly associated with shorter survival in patients with adenocarcinoma (log-rank P = 0.026) and remained an independent prognostic factor by multivariable analysis. Among the four assays, 22C3, 28-8 and SP263 were highly concordant for tumor cell scoring. With a cutoff of ≥50% (i.e., the threshold for first-line patient selection), inter-rater agreement was high among the three assays with percentage agreement >97%. In conclusion, three PD-L1 assays showed good analytical performance and a high agreement with each other, but not all cases were correctly classified using the same clinical cutoff. Further studies comparing the predictive value of these assays are required to address the interchangeability of these assays for clinical use.

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Author information


  1. Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, New Territories, Hong Kong

    • Anthony W. H. Chan
    • , Joanna H. M. Tong
    • , Johnny S. H. Kwan
    • , Chit Chow
    • , Lau Y. Chung
    • , Shuk L. Chau
    • , Raymond W. M. Lung
    •  & Ka F. To
  2. State Key Laboratory in Oncology in South China, The Chinese University of Hong Kong, New Territories, Hong Kong

    • Anthony W. H. Chan
    • , Joanna H. M. Tong
    • , Johnny S. H. Kwan
    • , Chit Chow
    • , Lau Y. Chung
    • , Shuk L. Chau
    • , Raymond W. M. Lung
    • , Tony S. K. Mok
    •  & Ka F. To
  3. Li Ka-Shing Institute of Health Sciences, The Chinese University of Hong Kong, New Territories, Hong Kong

    • Anthony W. H. Chan
    • , Joanna H. M. Tong
    • , Johnny S. H. Kwan
    • , Chit Chow
    • , Lau Y. Chung
    • , Shuk L. Chau
    • , Raymond W. M. Lung
    •  & Ka F. To
  4. Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, New Territories, Hong Kong

    • Calvin S. H. Ng
    •  & Innes Y. P. Wan
  5. Department of Clinical Oncology, The Chinese University of Hong Kong, New Territories, Hong Kong

    • Tony S. K. Mok


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Conflict of interest

Professor T.M. received grant or research support from AstraZeneca, BI, Pfizer, Novartis, SFJ, Roche, MSD, Clovis Oncology, BMS, Eisai, Taiho; Speaker’s fee from AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, MSD, Novartis, BMS, Taiho, Ariad/Takeda, Amgen; honoraria from AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, Merck Serono, MSD, Novartis, SFJ Pharmaceutical, ACEA Biosciences, Inc., Vertex Pharmaceuticals, BMS, OncoGenex Pharmaceuticals, Inc., Celgene, Ignyta, Inc., Fishawack Facilitate Ltd. He is a major stock shareholder on Sanomics Ltd. He serves as advisory board for AstraZeneca, Roche/Genentech, Pfizer, Eli Lilly, BI, Clovis Oncology, Merck Serono, MSD, Novartis, SFJ Pharmaceutical, ACEA Biosciences, Inc., Vertex Pharmaceuticals, BMS, geneDecode Co., OncoGenex Technologies Inc., Celgene, Ignyta, Inc., Cirina, Fishawack Facilitate Ltd and board director for IASLC, Chinese Lung Cancer Research Foundation Ltd., Chinese Society of Clinical Oncology (CSCO), Hong Kong Cancer Therapy Society (HKCTS). Professor A.W.H.C. serves as an advisor for Novartis. Professor C.S.H.N. serves as an advisor/consultant for Janssen Pharmaceutical, Inc. The remaining authors declare that they have no conflict of interest.

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Correspondence to Ka F. To.

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