Increased Immunohistochemical Expression of Stimulator of Interferon Genes (STING) in Renal Cancer with Venous Tumor Thrombus Is Associated with Worse Prognosis

TL;DR

High STING protein levels in kidney cancer with blood vessel spread are linked to worse survival, suggesting it could help predict outcomes.

Contribution

First study to show STING's prognostic value in kidney cancer with venous tumor thrombus.

Findings

STING expression in venous tumor thrombus correlates with worse overall survival.

Tumor-infiltrating leucocytes are strong prognostic indicators in both primary tumors and thrombus.

STING and PD-L1 expression are linked in primary tumor cells.

Abstract

Background/Objectives: We focused on the expression of a novel immune marker, cytoplasmic stimulator of interferon genes (STING), in the cohort of primary renal cell cancer (RCC) with venous tumor thrombus (VTT), in conjunction with the assessment of tumor-infiltrating leucocytes (TILs). Methods: The study group comprised 82 patients with clear cell RCC and VTT, operated on in the years 2012–2019 in two university urological centers. Tissue microarrays were constructed, and respective antibodies were used for staining purposes. The biomarkers were analyzed in primary RCC and VTT. Results: The frequency of STING expression in both analyzed compartments was similar (p = 0.18). Its presence correlated with no clinicopathological features but for necrosis in VTT only (p = 0.0023). PD-L1 expression in the primary tumor was associated with STING in tumor cells in the same compartment (p = 0.02). On the contrary, VISTA expression was correlated with the presence of STING in VTT. TIL presence was associated with positive PD-L1 (p = 0.008) and STING (p < 0.05) expression in the primary tumor. Strong STING expression in VTT was associated with inferior overall survival (OS) (p = 0.0061). TIL presence emerged as a robust prognostic factor for OS in both primary tumor (p = 0.021) and VTT (p = 0.034). Conclusions: We presented for the first time the prognostic values of STING in a contemporary cohort of RCC patients with VTT. STING expression in VTT showed prognostic potential, while TIL assessment proved to be a particularly valuable prognostic tool that can be readily implemented in routine pathological evaluation.

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