Research Papers:

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

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

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Oncotarget. 2021; 12:1580-1586. https://doi.org/10.18632/oncotarget.28029

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Janaina Mendes Ferreira1, Luiz Henrique Gomes Matheus1, Renato Vasconcelos Souza de Almeida3, Petronio Augusto de Souza Melo3, Kátia Ramos Moreira Leite2, Claudio Bovolenta Murta3, Joaquim Francisco de Almeida Claro3, Cleber Pinto Camacho1, José Pontes-Júnior2,3 and Humberto Dellê1

1 Postgraduate Program in Medicine, Universidade Nove de Julho, São Paulo, Brazil

2 Laboratory of Medical Investigation, Urology Department, University of São Paulo Medical School, São Paulo, Brazil

3 Divisão de Urologia do Centro de Saúde Masculina do Hospital Brigadeiro, São Paulo, Brazil

Correspondence to:

Janaina Mendes Ferreira,email: [email protected]

Keywords: bladder cancer; purinergic signaling; ectonucleotidases; CD39

Abbreviations: BC: bladder cancer; NMI: non-muscle-invasive; MI: muscle-invasive; TMA: Tissue microarray

Received: April 21, 2021     Accepted: July 13, 2021     Published: August 03, 2021

Copyright: © 2021 Ferreira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.

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