Background: Programmed death-ligand 1 (PD-L1) is a crucial biomarker predicting efficacious treatment of immune checkpoint inhibitors (ICIs). Understanding the genetic association of PD-L1 expression provides insights into the tumor-immune interaction and further exploration of immunotherapeutic biomarkers. However, the diverse and dissimilar quantifying assays might lead to inconsonant and confusing results, not conducive to the following research. Previous studies identified distinct staining utility among multiple PD-L1 antibodies, however, whether the genomic correlate of stained PD-L1 is also impacted by different testing assays is largely unknown.Methods: We evaluated 873 Chinese LUAD patients with lung adenocarcinoma in whom FDA-approved PD-L1 testing (22C3, Dako, Glostrup, Denmark; SP263, Ventana, Tucson, AZ) and targeted next-generation sequencing (3D Medicines Inc.) was performed on the same tissue. Data from Memorial Sloan Kettering Cancer Center (MSKCC), The Cancer Genome Atlas (TCGA) and the OAK trial were analyzed for further validation.Results: In the 3DMed database (n¼873), PD-L1 expression in tumor cells was positively correlated with tumor mutational burden. (p<0.001). PD-L1 positivity was more common in metastatic lymph nodes compared to primary lung tumors and other metastatic samples (p ¼0.009). Deleterious mutations in KRAS, TP53, ALK and MET significantly associated with PD-L1 high expression (each p<0.05) and EGFR and ERBB2 mutations associated with PD-L1 negativity (each p<0.05). Comparing the results in the 3DMed, MSKCC, TCGA, and OAK cohorts using different methods to quantifying PD-L1 expression, most of the positive results were validated in at least two cohorts, except ERBB2.
The COVID-19 pandemic presented numerous challenges to the continuity of programmed cell death ligand 1 (PD-L1) assay training events conducted by our organization. Under typical conditions, these training events are face-to-face affairs, where participants are trained to assay algorithms on glass slides during multi-headed scope sessions. Social distancing measures undertaken to slow pandemic spread necessitated the adaptation of our training methods to facilitate assay training and subsequent continuation of clinical trials. The present report details the creation and use of the Roche pathology training portal (PTP) that allowed for remote training to diagnostic assay algorithms. The PTP is a web-based system comprised of a learning management system (LMS) coupled to an image management system (IMS). Whole slide images (WSIs) were produced using a DP200 instrument (Roche, Pleasanton, CA) and these scan files were then uploaded to an IMS. Courses were created on the LMS using annotated WSIs that were shared with enrolled pathologists worldwide during assay training events. These courses culminated in assay certification examinations, where pathologists evaluated test-case WSIs and evaluated these cases within the LMS. Trainee submissions were analyzed for pass/fail status by comparing user data entries with consensus scores on these test-case WSIs. To date, 47 pathologist trainings have occurred and of these, 44 have successfully passed the associated assay certification exam on the first attempt (93% 1 st -try pass rate). The PTP allowed roche to continue training sites during the COVID-19 pandemic, and these early results demonstrate the capability of this digital solution regarding PD-L1 diagnostic assay training events.
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