The Reproducibility of Histopathologic Assessments of Programmed Cell Death-Ligand 1 Using Companion Diagnostics in NSCLC

INTRODUCTION: Accurate results on the status of programmed cell death-ligand 1 (PD-L1) rely on not only the quality of immunohistochemistry testing but also the accuracy of the pathologic assessments. We explored the intraobserver and interobserver reproducibility of the interpretations for the companion diagnostics, the Dako PD-L1 22C3 pharmDx kit (Dako North America, Inc, Carpinteria, CA) and the VENTANA PD-L1 (SP263, Ventana Medical Systems, Inc, Tucson, AZ) assay, and the consistency between microscopic and digital interpretations of PD-L1. METHODS: A total of 150 surgical specimens diagnosed as NSCLC 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. A total of 100 sections were stained with the 22C3 clone and scored for the interobserver reproducibility, 20 cases of which were interpreted twice to assess the intraobserver reproducibility, and 50 cases of which were scanned into digital images to measure the consistency between microscopic and digital interpretations. A total of 44 sections were stained with the SP263 clone and scored for the interobserver reproducibility. RESULTS: For the intraobserver reproducibility of 22C3, the overall percent agreements were 92.0% and 89.0% for binary tumor evaluation at the cutoffs of 1% and 50%, respectively. The reliability among the pathologists revealed a substantial agreement for 22C3, whereas it revealed a substantial agreement at the cutoff of 1% and moderate agreement at the cutoffs of 25% and 50% for SP263. Microscopic and digital interpretations of PD-L1 revealed good consistency. CONCLUSIONS: Intraobserver and interobserver reproducibility of the interpretations for 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 cutoffs, is essential for markedly improving such reproducibility. Digital imaging could improve the reproducibility of interpretation for PD-L1 among pathologists.