Clinical significance of tumoral PD-L1 expression in Wilms tumors

Abstract

Background: Although cure rate for Wilms tumor (WT) is high recent years, there is still small fraction of patients suffering from tumor relapse or metastases. It is urgent to identify more valuable biomarkers associated with disease progression. Previous studies have shown that PD-L1 was abnormally expressed in various type of cancers and acted as predictor for poor prognosis for those cancers. PD-1/PD-L1 inhibitors have achieved great success in various malignancies with correlation between PD-L1 expression and responses. We conducted this retrospective study to better understand the role of PD-L1 in WT development.

Objective: The aim of this study was to evaluate the expression rate of tumoral PD-L1 in WT and investigate the association of PD-L1 with tumor invasion and metastasis.

Study design: Seventy-seven patients with WT, including 20 cases of primary WTs with corresponding resected invasive/lymph node metastatic tumors were enrolled in the research. Immunohistochemistry was used to examine tumoral PD-L1 expression. Kaplan-Meier analysis with regard to the relationship between the expression of tumoral PD-L1 and follow-up information was performed.

Results: Positive expression rate of tumoral PD-L1 was 28.6% in primary WT tissues, while 35% in associated invasive/metastatic ones. The tumoral PD-L1 expression in primary WTs were correlated with late stage and unfavorable histology (P = 0.007; P = 0.002). The expression rate of tumoral PD-L1 was higher in the progression group than that without distant metastasis or relapse (P = 0.038). The expression rate of PD-L1 between primary WTs and matched invasive/metastatic tissues was concordant (P = 0.435). Tumoral PD-L1 expression was associated with disease-free survival (DFS) and overall survival (OS) (P = 0.02; P = 0.03). Tumor PD-L1 expression was associated with DFS and OS in univariable analyses but not in multivariable Cox regression, adjusting for histology and tumor stage.

Discussion: We found that PD-L1 expression was associated with the late-stage of WT and unfavorable histology, which were tightly associated with disease relapse and progression, predicting poor prognosis. The subsequent survival analysis also showed that PD-L1 expression was linked to both shorter DFS and OS. After adjustment for WT stage and histology, PD-L1 expression was no longer an independent predictor of DFS/OS. The value of PD-L1 as predictor for prognosis and potential therapeutic target in WT still need to be validated in large cohort in future.

Conclusion: Although PD-L1 expression correlated with established prognostic factors in our dataset, its value as a prognostic marker and therapeutic target, if any, remains to be shown in future.

Keywords: Invasion; Metastasis; Prognosis; Tumoral PD-L1; Wilms tumor.