NRF2 immunolocalization in human breast cancer patients as a prognostic factor

Yoshiaki Onodera, Hozumi Motohashi, Kiyoshi Takagi, Yasuhiro Miki, Yukiko Shibahara, Mika Watanabe, Takanori Ishida, Hisashi Hirakawa, Hironobu Sasano, Masayuki Yamamoto, Takashi Suzuki

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)


Nuclear factor erythroid 2-related factor 2 (NRF2 (NFE2L2)) is an important transcriptional activator involved in the cellular defense mechanisms against electrophilic and oxidative stress. Recent studies have demonstrated that the expression of NRF2 protein is upregulated in several human malignancies and is associated with worse prognosis in these patients. However, the pathological and clinical significance of NRF2 has remained largely unknown in breast cancer patients. Therefore, in this study, we immunolocalized NRF2 in 106 breast carcinoma cases. NRF2 immunoreactivity was mainly detected in the nucleus of the breast carcinoma cells and it was positive in 44% of the cases. NRF2 status was significantly associated with histological grade, Ki-67 labeling index, p62 immunoreactivity, and NAD(P) H:quinone oxidoreductase 1 (NQO1) immunoreactivity, and the results of multivariate analyses revealed that NRF2 status was an independent adverse prognostic factor for both recurrence and disease-free survival of the patients. Subsequent in vitro studies demonstrated that the expression of NRF2 significantly increased the proliferation activity of MCF7 and SK-BR-3 breast carcinoma cells. These results indicate that nuclear NRF2 protein plays important roles in the proliferation and/or progression of breast carcinoma, and nuclear NRF2 immunoreactivity is therefore considered a potent prognostic factor in breast cancer patients.

Original languageEnglish
Pages (from-to)241-252
Number of pages12
JournalEndocrine-Related Cancer
Issue number2
Publication statusPublished - 2014 Apr


  • Breast
  • Carcinoma
  • Immunohistochemistry
  • NRF2
  • Prognosis
  • Proliferation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research


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