Cell-type-specific CD73 expression is an independent prognostic factor in bladder cancer

CD73 is an adenosine-producing cell surface enzyme, which exerts strong anti-inflammatory and migration modulating effects in many cell types. We evaluated the potential of CD73 as a biomarker in predicting the outcome of bladder carcinoma. CD73 expression in tumor and stromal cells was analyzed using immunohistochemistry in 270 bladder cancer (BC) patients 166 non-muscle-invasive BC (NMIBC) and 104 muscle-invasive BC (MIBC) tumors. The correlations of CD73 with clinical and pathological characteristics were evaluated with Pearson's and Fischer's tests. The Kaplan-Meier method and Cox proportional hazards regression models were used to analyze the association between CD73 expression and outcome. CD73 expression showed substantial variation in basal and suprabasal layers of the cancerous epithelium, stromal fibroblasts, endothelial cells and lymphocytes in different tumor specimens. In log-rank analyses, CD73 expression in cancer cells associated with better survival both in NMIBC and MIBC, whereas CD73 positivity in stromal fibroblasts associated with impaired survival in NMIBC. In multivariable models, CD73 negative epithelial cells in both BC types and CD73 negative endothelial cells in MIBC were independent factors predicting poor outcome. We conclude that in contrast to many other cancer types, high CD73 expression in BC predicts favorable prognosis.