The reproducibility of histopathologic assessments of Programmed Cell Death Ligand-1 using companion diagnostics in non-small-cell lung cancer

Abstract Background Accurate results on the status of Programmed Cell Death Ligand-1 (PD-L1) rely on not only the quality of immunohistochemistry (IHC) testing, but also the accuracy of the pathologic assessments. We explored the intra- and inter-observer reproducibility of the interpretations for the companion diagnostics, the Dako PD-L1 22C3 pharmDx kit and the VENTANA PD-L1 (SP263) assay, and the consistency between microscopic and digital interpretations of PD-L1. Patients and methods One hundred and fifty surgical specimens diagnosed as non-small-cell lung cancer from December 2013 to July 2017 were included in this study. Twenty pathologists from different medical centers were enrolled to interpret the results of PD-L1 on the same day. One hundred sections were stained with the 22C3 clone and scored for the inter-observer reproducibility, 20 cases of which were interpreted twice to assess the intra-observer reproducibility, and 50 cases of which were scanned into digital images to measure the consistency between microscopic and digital interpretations. Forty-four sections were stained with the SP263 clone and scored for the inter-observer reproducibility. Results For the intra-observer reproducibility of 22C3, the overall percent agreements were 92.0% and 89.0% for binary tumor evaluation at the cut-offs of 1% and 50%. The reliability between pathologists showed “substantial” agreement for 22C3, while showing “substantial” agreement at the cut-off of 1% and “moderate” agreement at the cut-offs of 25% and 50% for SP263. Microscopic and digital interpretations of PD-L1 showed good consistency. Conclusions Intra- and inter-observer reproducibility of the interpretations for the PD-L1 was high using the 22C3 clone, but lower for the SP263 clone. Corresponding training on such assessments, especially on the cases around the specific cut-offs, is essential for markedly improving such reproducibility. Digital imaging could improve the reproducibility of interpretation for the PD-L1 among pathologists.