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Endocr Relat Cancer. 2014 Feb 27;21(2):241-52. doi: 10.1530/ERC-13-0234. Print 2014 Apr.

NRF2 immunolocalization in human breast cancer patients as a prognostic factor.

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  • 1Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan Department of Pathology and Histotechnology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi-ken 980-8575, Japan Department of Pathology, Tohoku University Hospital, Sendai, Japan Department of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan Department of Surgery, Tohoku Kosai Hospital, Sendai, Japan Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.

Abstract

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.

KEYWORDS:

NRF2; breast; carcinoma; immunohistochemistry; prognosis; proliferation

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