Clinicopathological implications of the expression of vascular endothelial growth factor and programmed cell death ligand 1 in clear cell renal cell carcinoma.

Combined anti-VEGF/anti-PD-L1 targeted therapy synergistically improves treatment outcomes in advanced renal cell carcinoma (RCC) compared with anti-PD-L1 or anti-VEGF monotherapy. Here, we analyzed the expression of VEGF and PD-L1 (SP142) in a retrospective cohort of 513 patients with clear cell (cc) RCC. PD-L1 expression on tumor cells (TCs) and immune cells (ICs) was evaluated by immunohistochemistry (IHC) with a positive threshold value of >/= 1%. Positive staining for PD-L1 on ICs and TCs was found in 115 (22.4%) and 7 (1.4%) cases, respectively. Moderate or strong staining for VEGF on TCs was found in 217 (42.3%) patients. PD-L1 expression on ICs and TCs was positively associated with VEGF expression on TCs. Both VEGF and PD-L1 (IC) positivity (VEGF/PD-L1 (IC): +/+) were observed in 65 (12.7%) cases. Patients in this subgroup exhibited more aggressive clinicopathologic features, including older age, higher WHO/ISUP grade, angiolymphatic invasion, tumor necrosis, and sarcomatoid differentiation (P < 0.05). Kaplan-Meier analysis indicated that expression of VEGF and PD-L1 on ICs was positively correlated with tumor recurrence (P < 0.001), whereas expression of PD-L1 on TCs was not (P = 0.554). Tumors with positivity for both antibodies (VEGF/PD-L1(IC): +/+) exhibited the worst recurrence-free survival (P < 0.001), and double positivity independently predicted tumor recurrence in ccRCC. The present study provides comprehensive and basic information about VEGF and PD-L1 expression for new combined therapy in primary ccRCC.