University of Wisconsin School of Medicine and Public Health
Introduction: Prior studies have evaluated PD-L1 expression as a prognostic biomarker for renal cell carcinoma (RCC) with mixed results when sampling only one region of large, heterogeneous tumors. The purpose of this study was to investigate PD-L1 expression using multi-region sampling to evaluate intra-tumor heterogeneity and ability to predict metastatic progression following radical nephrectomy for localized disease. Methods: RCC tumor tissue microarrays (TMAs) were constructed for non-metastatic RCC patients treated with nephrectomy. Two cohorts of patients were selected, those that progressed to metastatic disease and those that did not. The cohorts were matched for age, gender, performance status, pT-stage, grade, tumor diameter and presence of tumor thrombus. From each tumor, a minimum of 10 tissue cores were analyzed. PD-L1 tissue expression was quantified as optical density (OD) per unit area using the Vectra system and InForm software (version 2.4). PD-L1 expression heterogeneity was evaluated with Kernel-density plots and compared between patients who progressed to metastatic RCC vs patients who remained disease free using nested t-tests. Results: TMAs were constructed for 46 patients. There were no differences in matching characteristics between groups. Metastatic progression was identified in 26 patients with median follow-up of 7 years (IQR 5-11). Twenty patients remained disease free with median follow-up of 11 years (IQR 8-15). Median tumor size was 9cm in both cohorts (P=0.2). Kernel-density plots demonstrated greater variance in PD-L1 expression among recurrent tumors (Fig 1A). Mean and standard deviation of the PD-L1 OD was higher for recurrent patients (mean OD 0.025 vs 0.011, P<0.001) (Fig 1B). When stratified by median PD-L1 OD, the median recurrence free survival for high PD-L1 expressing tumors was 11.7 months and was not reached for low PD-L1 expressing tumors (P <0.001) (Fig 1C). Conclusions: PD-L1 expression varies substantially throughout individual tumors. Multi-region sampling helps account for PD-L1 tumor heterogeneity, and PD-L1 expression predicted metastatic progression following radical nephrectomy for localized disease. Further studies are required to validate these findings. SOURCE OF Funding: None
.jpg "Daniel Shapiro, MD (he/him/his) photo")
