TY - JOUR
T1 - Multicentre study on the consistency of PD-L1 immunohistochemistry as predictive test for immunotherapy in non-small cell lung cancer
AU - Butter, Rogier
AU - A'T Hart, Nils
AU - Hooijer, Gerrit K.J.
AU - Monkhorst, Kim
AU - Speel, Ernst Jan
AU - Theunissen, Paul
AU - Thunnissen, Erik
AU - Von Der Thüsen, Jan H.
AU - Timens, Wim
AU - Van De Vijver, Marc J.
AU - Hart't, Nils A.
N1 - Funding Information: Funding This study was funded by Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Competing interests RB: none. N’tH: MSD (unrestricted grant), Pfizer (personal fee). KM: Roche (research grant, personal fee), MSD (research grant, personal fee), Astra Zeneca (research grant, personal fee), Pfizer (personal fee), Benecke (personal fee), BMS (personal fee), Abbvie (personal fee), Diaceutics (personal fee). E-JS: MSD (research grant, personal fee), BMS (research grant, personal fee), Novartis (research grant), AstraZeneca (research grant), AbbVie (personal fee), Bayer (personal fee), Roche (personal fee). ET: HistoGeneX (personal fee), Roche Diagnostics (personal fee). JHVdT: Astellas (research grant), BMS (research grant, personal fee), AbbVie (personal fee), Astra Zeneca (personal fee), Boehringer-Ingelheim (personal fee), BMS (personal fee), Eli Lilly (personal fee), MSD (personal fee), Pfizer (personal fee), Roche (personal fee). WT: MSD (personal fee), Roche-Ventana (personal fee), Pfizer (personal fee), Astra Zeneca (personal fee), GSK (personal fee), Chiesi (personal fee), Dutch Asthma Fund (research grant), Biotest (personal fee), Novartis (personal fee), Lilly Oncology (personal fee), Boehringer Ingelheim (personal fee). MJvdV: MSD (research grant), Roche (personal fee). Publisher Copyright: © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Aims Investigate the impact of interlaboratory-and interobserver variability of immunohistochemistry on the assessment of programmed death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). Methods Two tissue microarrays (TMAs) were constructed from 50 (TMA-A) and 51 (TMA-B) resected NSCLC cases, and distributed among eight centres. Immunostaining for PD-L1 was performed using Agilent's 22C3 pharmDx Assay (pharmDx) and/or a 22C3 laboratory developed test (LDT). The interlaboratory variability of staining-and interobserver variability of scoring for PD-L1 were assessed in selected critical samples (samples at the cut-off of positivity) and non-critical samples. Also, PD-L1 epitope deterioration in time in stored unstained slides was analysed. Krippendorff's alpha values (0=maximal, 1=no variability) were calculated as measure for variability. Results For interlaboratory variability of immunostaining, the percentage of PD-L1 positive cases among centres ranged 40%-51% (1% cut-off) and 23%-30% (50% cut-off). Alpha values at 1% cut-off were 0.88 (pharmDx) and 0.87 (LDT) and at 50% cut-off 0.82 (pharmDx) and 0.95 (LDT). Interobserver variability of scoring resulted in PD-L1 positive cases ranging 29%-55% (1% cut-off) and 14%-30% (50% cut-off) among pathologists. Alpha values were at 1% cut-off 0.83 (TMA-A) and 0.66 (TMA-B), and at 50% cut-off 0.77 (TMA-A) and 0.78 (TMA-B). Interlaboratory variability of staining was higher (p<0.001) in critical samples than in non-critical samples at 50% cut-off. Furthermore, PD-L1 epitope deterioration in unstained slides was observed after 12 weeks. Conclusions The results provide insight in factors contributing to variability of immunohistochemical assessment of PD-L1, and contribute to more reliable predictive testing for PD-L1.
AB - Aims Investigate the impact of interlaboratory-and interobserver variability of immunohistochemistry on the assessment of programmed death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). Methods Two tissue microarrays (TMAs) were constructed from 50 (TMA-A) and 51 (TMA-B) resected NSCLC cases, and distributed among eight centres. Immunostaining for PD-L1 was performed using Agilent's 22C3 pharmDx Assay (pharmDx) and/or a 22C3 laboratory developed test (LDT). The interlaboratory variability of staining-and interobserver variability of scoring for PD-L1 were assessed in selected critical samples (samples at the cut-off of positivity) and non-critical samples. Also, PD-L1 epitope deterioration in time in stored unstained slides was analysed. Krippendorff's alpha values (0=maximal, 1=no variability) were calculated as measure for variability. Results For interlaboratory variability of immunostaining, the percentage of PD-L1 positive cases among centres ranged 40%-51% (1% cut-off) and 23%-30% (50% cut-off). Alpha values at 1% cut-off were 0.88 (pharmDx) and 0.87 (LDT) and at 50% cut-off 0.82 (pharmDx) and 0.95 (LDT). Interobserver variability of scoring resulted in PD-L1 positive cases ranging 29%-55% (1% cut-off) and 14%-30% (50% cut-off) among pathologists. Alpha values were at 1% cut-off 0.83 (TMA-A) and 0.66 (TMA-B), and at 50% cut-off 0.77 (TMA-A) and 0.78 (TMA-B). Interlaboratory variability of staining was higher (p<0.001) in critical samples than in non-critical samples at 50% cut-off. Furthermore, PD-L1 epitope deterioration in unstained slides was observed after 12 weeks. Conclusions The results provide insight in factors contributing to variability of immunohistochemical assessment of PD-L1, and contribute to more reliable predictive testing for PD-L1.
KW - histopathology
KW - immunohistochemistry
KW - lung cancer
KW - oncology
KW - pulmonary pathology
UR - http://www.scopus.com/inward/record.url?scp=85076376142&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/jclinpath-2019-205993
DO - https://doi.org/10.1136/jclinpath-2019-205993
M3 - Article
C2 - 31822512
SN - 0021-9746
VL - 73
SP - 423
EP - 430
JO - Journal of clinical pathology
JF - Journal of clinical pathology
IS - 7
ER -