Pan-cancer landscape of (PD-L1) copy number changes in 244 584 patient samples and the correlation with PD-L1 protein expression.

INTRODUCTION

Several studies have shown clinical outcomes data that support the use of ) copy-number (CN) gains and/or losses as a biomarker for immune checkpoint inhibitor (ICPI). Here, we present the landscape of CN changes across a large cohort of solid tumor cases and correlate these with PD-L1 protein expression by immunohistochemistry.

METHODS

We analyzed all cases that underwent comprehensive genomic profiling (CGP) testing at Foundation Medicine between August 2014 and June 2020. CN changes were correlated with PD-L1 expression in tumor types where there were Food and Drug Administration approved companion diagnostic (CDx) claims and the CDx assay was used to assess PD-L1 expression.

RESULTS

In all, 244 584 samples representing 290 solid tumor types were included in the study. Overall, 17.6% (42 983/244 584) had CN gains (>specimen ploidy), 44.6% (108 970/244 584) were CN neutral, and 37.9% (92 631/244 584) had CN loss. Using different CN cut offs to define positivity resulted in different prevalence estimates: ploidy +1, 17.4% (42 636/244 584); ploidy +2, 6.2% (15 183/244 584); ploidy +3, 2.2% (5375/244 584); ploidy +4, 1.1% (2712/244 584); and ploidy +8, 0.2% (434/244 584). The prevalence of CN changes and CN positivity varied based on tumor type. CN gains were significantly associated with PD-L1 positivity in NSCLC, urothelial carcinoma, breast carcinoma, cervical carcinoma, esophagus squamous cell carcinoma (SCC) and head and neck SCC (ORs 3.3, 3.0, 2.0, 4.5. 3.8, 8.4, 1.4, respectively; p<0.05) and with microsatellite instability status in only clinically relevant tumor types (gastric adenocarcinoma, colorectal adenocarcinoma, uterine endometrial adenocarcinoma, esophageal adenocarcinoma and gastroesophageal junction adenocarcinoma (OR: 5.2, 1.9, 3.2, 3.7 and 6.5, respectively; p<0.05)). Conversely, CN changes were not significantly correlated with tumor mutational burden in almost all the tumor types.

CONCLUSION

CN changes and PD-L1 expression were highly correlated in multiple tumor types. These prevalence data on CN changes across a large cohort of different solid tumors can be used to design future clinical studies to assess whether CN changes could be a potential biomarker for ICPI.