@article{3121206,
    title = "Programmed death-ligand 1 expression influenced by tissue sample size. Scoring based on tissue microarrays’ and cross-validation with resections, in patients with, stage I–III, non-small cell lung carcinoma of the European Thoracic Oncology Platform Lungscape cohort",
    author = "Thunnissen, E. and Kerr, K.M. and Dafni, U. and Bubendorf, L. and Finn, S.P. and Soltermann, A. and Biernat, W. and Cheney, R. and Verbeken, E. and Warth, A. and Marchetti, A. and Speel, E.-J.M. and Pokharel, S. and Quinn, A.M. and Monkhorst, K. and Navarro, A. and Madsen, L.B. and Tsourti, Z. and Geiger, T. and Kammler, R. and Peters, S. and Stahel, R.A. and Rosell, R. and Blackhall, F. and Molina, M.A. and Weder, W. and Finn, S. and Hiltbrunner, A. and Marti, N. and Polydoropoulou, V. and Zygoura, P. and Nicolson, M. and Stevenson, D.A.J. and Mathieson, W. and Smit, E. and Radonic, T. and Rulle, U. and Curioni, A. and Gray, S.G. and Gately, K. and Barr, M. and Meldgaard, P. and Madsen, L.B. and Savic, S. and Lardinois, D. and Nackaerts, K. and Dooms, C. and Wauters, E. and Van Der Borght, S. and Wrona, A. and Rzyman, W. and Jassem, J. and Dienemann, H. and Muley, T. and De Luca, G. and di Lorito, A. and Dingemans, A.-M. and Ruland, A. and Ferenczy, P. and Franklin, L. and Baas, P. and van de Wiel, B. and Camps, C. and Martorell, M. and for the European Thoracic Oncology Platform Lungscape Consortium",
    journal = "Modern Pathology",
    year = "2020",
    volume = "33",
    number = "5",
    pages = "792-801",
    publisher = "Springer Nature BV",
    issn = "0893-3952, 1530-0285",
    doi = "10.1038/s41379-019-0383-9",
    keywords = "programmed death 1 ligand 1;  CD274 protein, human;  programmed death 1 ligand 1;  tumor marker, Article;  cancer classification;  cancer staging;  cancer surgery;  clinical feature;  cohort analysis;  controlled study;  cross validation;  diagnostic accuracy;  human;  human tissue;  immunohistochemistry;  non small cell lung cancer;  postoperative complication;  priority journal;  protein expression;  randomized controlled trial;  retrospective study;  sensitivity and specificity;  tissue microarray;  tumor biopsy;  tumor volume;  biopsy;  biosynthesis;  health care quality;  lung tumor;  non small cell lung cancer;  pathology;  procedures;  tissue microarray, B7-H1 Antigen;  Biomarkers, Tumor;  Biopsy;  Carcinoma, Non-Small-Cell Lung;  Cohort Studies;  Humans;  Lung Neoplasms;  Quality Assurance, Health Care;  Retrospective Studies;  Tissue Array Analysis",
    abstract = "PD-L1, as assessed by immunohistochemistry, is a predictive biomarker for immuno-oncology treatment in lung cancer. Different scoring methods have been used to assess its status, resulting in a wide range of positivity rates. We use the European Thoracic Oncology Platform Lungscape non-small cell lung carcinoma cohort to explore this issue. PD-L1 expression was assessed via immunohistochemistry on tissue microarrays (up to four cores per case), using the DAKO 28-8 immunohistochemistry assay, following a two-round external quality assessment procedure. All samples were analyzed under the same protocol. Cross-validation of scoring between tissue microarray and whole sections was performed in 10% randomly selected samples. Cutoff points considered: ≥1, 50 (primarily), and 25%. At the two external quality assessment rounds, tissue microarray scoring agreement rates between pathologists were: 73% and 81%. There were 2008 cases with valid immunohistochemistry tissue microarray results (50% all cores evaluable). Concordant cases at 1, 25, and 50% were: 85, 91, and 93%. Tissue microarray core results were identical for 70% of cases. Sensitivity of the tissue microarray method for 1, 25, and 50% was: 80, 78, and 79% (specificity: 90, 95, 98%). Complete agreement between tissue microarrays and whole sections was achieved for 60% of the cases. Highest sensitivity rates for 1% and 50% cutoffs were detected for higher number of cores. Underestimation of PD-L1 expression on small samples is more common than overestimation. We demonstrated that classification of PD-L1 on small biopsy samples does not represent the overall expression of PD-L1 in all non-small cell cancer carcinoma cases, although the majority of cases are ‘correctly’ classified. In future studies, sampling more and larger biopsies, recording the biopsy size and tumor load may permit further refinement, increasing predictive accuracy. © 2019, The Author(s), under exclusive licence to United States & Canadian Academy of Pathology."
}