The reproducibility of PD-L1 scoring in lung cancer: can the pathologists do better?

In the era of personalized medicine, the selection of advanced stages non-small cell lung cancer (NSCLC) patients for targeted treatments requires development, validation and continuous quality assessments of a wide array of laboratory assays, including both conventional and developing methodologies. While high throughput molecular testing approaches, to extensively assess genomic biomarkers of current and potential clinical value, are fascinating innovations in the field of modern oncology, traditional morpho-molecular methodologies such as fluorescent in situ hybridisation and immunohistochemical (IHC) techniques are still precious in the clinic to guide therapeutic interventions (1). This holds even more true, when considering the recent requirements to evaluate in NSCLC cells the checkpoint inhibitor programmed cell death ligand 1 (PD-L1) protein expression. Different primary antibody clones, raised against different epitopes (parts) of the PD-L1, are available (2). Each clone is linked to a specific treatment: clone 28-8 (Dako, Glostrup, Denmark) for nivolumab, 22C3 (Dako) for pembrolizumab, SP142 (Ventana, Tucson, AZ, USA) for atezolizumab and SP263 (Ventana) for durvalumab. Different clinical trial performed its own PD-L1 immunohistochemistry assay as a prepackaged kit of reagents running on company-specific staining platforms according to the manufacturers’ instructions either on the Dako Link AS-48 (no longer available commercially) or on the Ventana Benchmark autostainer systems, adopting custom scoring-criteria for each assay (2).