High CD39 expression is associated with the non-muscle-invasive phenotype of human bladder cancer.

Janaina Mendes Ferreira,Luiz Henrique Gomes Matheus,Petronio Augusto De Souza Melo,Cleber Pinto Camacho,Joaquim Francisco De Almeida Claro,Humberto Dellê,Claudio Bovolenta Murta,Renato Vasconcelos Souza De Almeida,José Pontes-Júnior,Kátia Ramos Moreira Leite

doi:10.18632/oncotarget.28029

Janaina Mendes Ferreira, Luiz Henrique Gomes Matheus + Show 8 more

Open Access

https://doi.org/10.18632/oncotarget.28029

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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, has been proposed to be used for prognosis of solid tumor. In BC this is not yet clear.Objective: 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.Materials and Methods: Retrospective clinical follow-up data and primary urothelial BC specimens of 162 patients were used (87 from patients who underwent transurethral resection and 75 from cystectomized patients). 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 CD73 expression was not powerful to predict the stage of BC. The association of both markers confirmed that only CD39 has potential in BC prognosis.Conclusions: The altered expression of CD39 presented herein supports the idea that this ectonucleotidase may be involved in bladder tumorigenesis. High expression of CD39 in tumor cells is correlated with the early stage of BC.

Highlights

Bladder cancer (BC) is the most common malignancy of the urinary tract, being the fourth most common cancer in men and the ninth in women [1]
CD39 immunoreactivity in bladder cancer (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 CD73 expression was not powerful to predict the stage of BC

Summary

Introduction

Bladder cancer (BC) is the most common malignancy of the urinary tract, being the fourth most common cancer in men and the ninth in women [1]. MI BC is a more aggressive disease, being associated with a 5-years survival rate of 60% and 10% for patients with localized disease and metastases, respectively [2] In these cases, radical cystectomy is often necessary. The equilibrium of the purinergic signals is acquired by the conversion of ATP/ADP to AMP and AMP to adenosine, which occurs by hydrolytic enzymes [3]. One of these enzymes is the CD39 (ecto-nucleoside triphosphate diphosphohydrolase-1, NTPDase-1), an integral membrane protein that hydrolyzes ATP and ADP in order to yield AMP in the extracellular space [4].

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