CD73 expression in primary and metastatic renal cell carcinoma (RCC).

643 Background: Agents targeting the PD-1 pathway have improved outcomes in RCC. CD73 may be an additional mechanism which tumors can exploit for immune evasion. It is regulated by hypoxia inducible factor (HIF) and converts AMP to adenosine. The resulting increase in extracellular adenosine can inhibit T-cell effector function. We evaluated CD73 expression in primary and metastatic tumor samples in patients with RCC. Methods: A commercial TMA (US Biomax) consisting of 31 primary clear cell RCC samples (2 with sarcomatoid features) with 8 matched and 1 unmatched metastases was used to assess CD73 expression. A genitourinary pathologist (OH) confirmed pathology and grade. Immunohistochemistry (IHC) was performed using a monoclonal anti-CD73 antibody (Cell Signaling; D7F9A). A combined score (CS: % of cells positive x intensity) was employed to quantify CD73 expression. Expression levels between matched primary and metastatic tissue was compared using Wilcoxon signed-rank test. Correlation of CD73 expression (CS > 0) in primary tumor with baseline clinical and pathologic characteristics was assessed using Kruskal-Wallis and Fisher's exact tests. Overall survival (OS) was estimated using the Kaplan-Meier method. Comparison between CD73 expression groups used log rank test. Results: CD73 expression was seen in 19% (n = 6) of primary and 66.7% (n = 6) of metastatic samples. Among matched primary and metastatic samples (n = 8 each), median CS was 25 (Q1-Q3:0-105) in metastatic samples while none of the corresponding primary samples demonstrated CD73 expression (median CS = 0, p = 0.062). CD73 expression in primary tumor samples did not correlate with baseline clinical or pathologic features. Five-year OS was 50% in patients who expressed CD73 in primary tumors compared to 84% in those who did not (p = 0.26). Conclusions: We observed a numerical increase in CD73 expression in metastatic tissue compared to primary RCC samples and worse 5 year OS. The small number of samples has limited statistical significance. Further studies are needed to examine the impact of CD73 expression on outcomes in RCC patients treated with currently approved checkpoint inhibitors and the investigational CD73 antagonists that are in early phases of development.