Expression balance of ectoenzymes CD39 and CD73 predicts invasiveness in human bladder cancer

Abstract Background An accurate prediction of progression is critical to define the management of bladder cancer (BC). The ectonucleotidases CD39 and CD73 play strategic roles in calibrating purinergic signals via an extracellular balance between ATP and adenosine. The altered expression of these enzymes plays a potential role in tumor invasion and metastasis, therefore, it has been proposed in the prognosis of solid tumors. In BC this is not yet clear. This study aimed to evaluate CD39 and CD73 expression in a cohort of patients with non-muscle-invasive (NMI) and muscle-invasive (MI) BC regard to its association with clinicopathological features. Methods Retrospective clinical follow-up data and primary urothelial BC specimens of 162 patients were used. Tissue microarrays were constructed, and immunohistochemistry for CD39 and CD73 was performed to make associations with clinicopathological data. Results Overall, 96 were NMI (59.3%) and 66 MI (40.7%). CD39 immunoreactivity in BC cells was found in 72% of the cases, while CD73 was found in 97%. High CD39 expression alone was more frequent in NMI BC (p < 0.001), while high expression of CD73 was more frequent in MI BC. The association of both markers potentiated the prediction, in that high CD39 expression and low CD73 expression was strongly associated with NMI BC and low CD39 with high CD73 was associated with MI BC. Conclusion The invasiveness stage of BC may be predicted by the altered expression of CD39 and CD73. Therefore CD39 serves as an additional tool for the selection of patients with favorable prognosis.