Expression of Nrf2 and NF-κB transcription factors in breast cancer and breast fibroadenoma: Insights for a new therapeutic approach

Abstract

// Camila Maria Simplicio-Revoredo 1 , Renato de Oliveira Pereira 2 , Mariella de Almeida Melo 2 , Pedro Vitor Lopes-Costa 2 , 3 , Paulo de Tarso Moura-Borges 3 , Emerson Brandão Sousa 3 , Fidelis Manes Neto 2 , Viriato Campelo 2 , Ione Maria Ribeiro Soares-Lopes 2 , Maria da Conceição Barros-Oliveira 1 , Cleciton Braga Tavares 1 , Alesse Ribeiro dos Santos 3 , Camila Guedes Borges de Araújo 2 , Eid Gonçalves Coelho 1 , Larysse Cardoso Campos-Verdes 1 , Aldenora Oliveira do Nascimento-Holanda 2 , Jackeline Lopes Viana 3 , Maria Liduina Meneses Bezerra-Chaves 3 , Rodrigo José de Vasconcelos-Valença 2 , Lina Gomes dos Santos 1 , Lauro Rodolpho Soares-Lopes 2 , André Luiz Pinho-Sobral 3 , Luiz Henrique Gebrim 1 and Benedito Borges da Silva 1 , 2 , 3 1 Postgraduate Program, Northeast Biotechnology Network (RENORBIO), Department of Health, Federal University of Piauí, Teresina, Piauí 64000-020, Brazil 2 Postgraduate Program in Health Sciences, Department of Mastology, Federal University of Piauí, Teresina, Piauí 64000-020, Brazil 3 Getúlio Vargas Hospital, Department of Mastology, Federal University of Piauí, Teresina, Piauí 64000-020, Brazil Correspondence to: Benedito Borges da Silva, email: beneditoborges@globo.com Keywords: breast cancer; fibroadenoma; NRF2; NF-κB; immunohistochemistry Received: November 25, 2019     Accepted: April 03, 2020     Published: May 05, 2020 ABSTRACT Background: Cancer and fibroadenoma are the most common breast tumors in women of reproductive age. Nuclear factor erythroid 2-related factor 2 (Nrf2) and the nuclear factor kappaB (NF-κB) transcription factor play an important role in the inflammatory process and in cell proliferation. However, few studies have analyzed these markers in breast cancer and fibroadenoma in women of reproductive age. Results: Light microscopy showed a higher concentration of anti-Nrf2 and anti-NF-κB-stained nuclei in breast cancer than in fibroadenoma. The mean percentage of stained nuclei for Nrf2 was 7.12 ± 5.2 and 43.21 ± 19.83 in the control and study groups, respectively (p < 0.0001). The mean percentage of anti-NF-κB was 10.75 ± 7.09 and 56.14 ± 21.19 (mean ± standard deviation) in the control and study groups, respectively (p < 0.0001). Histological grade 3 tumors showed a significantly higher expression of Nrf2 and NF-κB than grade 1 tumors (p < 0.05). Material and methods: This study was approved by the Institutional Review Board of Federal University of Piaui and all patients assigned an inform consent term prior to the study initiation. Nrf2 and NF-κB expression was evaluated by immunohistochemistry in 66 patients, divided into two groups, control (fibroadenoma, n = 36) and study (cancer, n = 30). The data were analyzed using ANOVA test and the statistical significance was established at p < 0.05. Conclusion: Nrf2 and NF-κB expression was significantly higher in breast cancer than in fibroadenoma, in addition to having a greater association with more aggressive tumors.