Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2018 Sep;13(9):1302-1311.
doi: 10.1016/j.jtho.2018.05.013. Epub 2018 May 22.

PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples: Results of Blueprint Phase 2 Project

Ming Sound Tsao  1 , Keith M Kerr  2 , Mark Kockx  3 , Mary-Beth Beasley  4 , Alain C Borczuk  5 , Johan Botling  6 , Lukas Bubendorf  7 , Lucian Chirieac  8 , Gang Chen  9 , Teh-Ying Chou  10 , Jin-Haeng Chung  11 , Sanja Dacic  12 , Sylvie Lantuejoul  13 , Mari Mino-Kenudson  14 , Andre L Moreira  15 , Andrew G Nicholson  16 , Masayuki Noguchi  17 , Giuseppe Pelosi  18 , Claudia Poleri  19 , Prudence A Russell  20 , Jennifer Sauter  21 , Erik Thunnissen  22 , Ignacio Wistuba  23 , Hui Yu  24 , Murry W Wynes  25 , Melania Pintilie  26 , Yasushi Yatabe  27 , Fred R Hirsch  28
Affiliations
Clinical Trial

PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples: Results of Blueprint Phase 2 Project

Ming Sound Tsao et al. J Thorac Oncol. 2018 Sep.

Abstract

Objectives: The Blueprint (BP) Programmed Death Ligand 1 (PD-L1) Immunohistochemistry Comparability Project is a pivotal academic/professional society and industrial collaboration to assess the feasibility of harmonizing the clinical use of five independently developed commercial PD-L1 immunohistochemistry assays. The goal of BP phase 2 (BP2) was to validate the results obtained in BP phase 1 by using real-world clinical lung cancer samples.

Methods: BP2 were conducted using 81 lung cancer specimens of various histological and sample types, stained with all five trial-validated PD-L1 assays (22C3, 28-8, SP142, SP263, and 73-10); the slides were evaluated by an international panel of pathologists. BP2 also assessed the reliability of PD-L1 scoring by using digital images, and samples prepared for cytological examination. PD-L1 expression was assessed for percentage (tumor proportional score) of tumor cell (TC) and immune cell areas showing PD-L1 staining, with TCs scored continuously or categorically with the cutoffs used in checkpoint inhibitor trials.

Results: The BP2 results showed highly comparable staining by the 22C3, 28-8 and SP263 assays; less sensitivity with the SP142 assay; and higher sensitivity with the 73-10 assay to detect PD-L1 expression on TCs. Glass slide and digital image scorings were highly concordant (Pearson correlation >0.96). There was very strong reliability among pathologists in TC PD-L1 scoring with all assays (overall intraclass correlation coefficient [ICC] = 0.86-0.93), poor reliability in IC PD-L1 scoring (overall ICC = 0.18-0.19), and good agreement in assessing PD-L1 status on cytological cell block materials (ICC = 0.78-0.85).

Conclusion: BP2 consolidates the analytical evidence for interchangeability of the 22C3, 28-8, and SP263 assays and lower sensitivity of the SP142 assay for determining tumor proportion score on TCs and demonstrates greater sensitivity of the 73-10 assay compared with that of the other assays.

Keywords: Checkpoint inhibitors; Companion diagnostics; Complementary diagnostics; Cytology; Immunooncology; Pathology.

PubMed Disclaimer

Conflict of interest statement

The remaining authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
Reliability of scoring tumor cells programmed death ligand 1 expression with use of Fleiss k statistics at cutoffs 1%, 25%, and 50% for digital and glass slide readings, respectively, and for all cases (the whole cohort) or NSCLC only, with cytological specimens excluded.
Figure 2.
Figure 2.
Comparability of programmed death ligand 1 staining on tumor cells among the five assays: overall comparison (A) and pairwise comparisons (B).
Figure 3.
Figure 3.
A representative case comparing the programmed death ligand 1 staining on the basis of the five assays.
Figure 4.
Figure 4.
Agreement of scoring tumor cells’ programmed death ligand 1 expression in NSCLC cytological specimens at different cutoffs.
See this image and copyright information in PMC

Comment in

References

    1. Gong J, Chehrazi-Raffle A, Reddi S, Salgia R. Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations. J Immunother Cancer. 2018;6:8. - PMC - PubMed
    1. Melosky B, Chu Q, Juergens R, Leighl N, McLeod D, Hirsch V. Pointed progress in second-line advanced non-small-cell lung cancer: the rapidly evolving field of checkpoint inhibition. J Clin Oncol. 2016;34:1676–1688. - PubMed
    1. Assi HI, Kamphorst AO, Moukalled NM, Ramalingam SS. Immune checkpoint inhibitors in advanced non-small cell lung cancer. Cancer. 2018;124:248–261. - PubMed
    1. Buttner R, Gosney JR, Skov BG, et al.Programmed death-ligand 1 immunohistochemistry testing: a review of analytical assays and clinical implementation in nonsmall-cell lung cancer. J Clin Oncol. 2017;35:3867–3876. - PubMed
    1. Yu H, Boyle TA, Zhou C, Rimm DL, Hirsch FR. PD-L1 expression in lung cancer. J Thorac Oncol. 2016;11: 964–975. - PMC - PubMed

Publication types