University of Oulu

Kari E, Teppo H-R, Haapasaari K-M, et al. J Clin Pathol 2019; 72 :316–321.

Nuclear factor erythroid 2-related factors 1 and 2 are able to define the worst prognosis group among high-risk diffuse large B cell lymphomas treated with R-CHOEP

Saved in:
Author: Kari, Esa1,2; Teppo, Hanna-Riikka1,3; Haapasaari, Kirsi-Maria3;
Organizations: 1Cancer Research and Translational Medicine Research Unit, University of Oulu, Oulu, Finland
2Department of Oncology and Radiotherapy, Oulu University Hospital, Oulu, Finland
3Department of Pathology, Oulu University Hospital, Oulu, Finland
4Department of Oncology and Radiotherapy, Oulu University Hospital, Oulu, Finland
5Department of Pathology, North Karelia Central Hospital, Joensuu, Finland
6Department of Pathology and Forensic Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland
7Department of Internal Medicine, Institute of Clinical Medicine, Kuopio University Hospital, Kuopio, Finland
8Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
9Department of Oncology, Kuopio University Hospital, Kuopio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.6 MB)
Persistent link:
Language: English
Published: BMJ, 2019
Publish Date: 2019-07-01


Aims: Oxidative stress markers and antioxidant enzymes have previously been shown to have prognostic value and associate with adverse outcome in patients with diffuse large B cell lymphoma (DLBCL). Nuclear factor erythroid 2-related factor 1 (Nrf1) and factor 2 (Nrf2) are among the principal inducers of antioxidant enzyme production. Kelch ECH associating protein 1 (Keap1) is a negative regulator of Nrf2, and BTB (BR-C, ttk and bab) domain and CNC homolog 1 (Bach1) represses the function of both factors. Their significance in DLBCL prognosis is unknown.

Methods: Diagnostic biopsy samples of 76 patients with high-risk DLBCL were retrospectively stained with immunohistochemistry for Nrf1, Nrf2, Keap1 and Bach1, and correlated with clinical data and outcome.

Results: Nuclear Nrf2 and nuclear Bach1 expression were associated with adverse clinical features (anaemia, advanced stage, high IPI, high risk of neutropaenic infections), whereas cytoplasmic Nrf1 and Nrf2 were associated with favourable clinical presentation (normal haemoglobin level, no B symptoms, limited stage). None of the evaluated factors could predict survival alone. However, when two of the following parameters were combined: high nuclear score of Nrf2, low nuclear score of Nrf1, high cytoplasmic score of Nrf1 and low cytoplasmic score of Keap1 were associated with significantly worse overall survival.

Conclusions: Nrf1 and Nrf2 are relevant in disease presentation and overall survival in high-risk DLBCL. Low nuclear expression of Nrf1, high cytoplasmic expression of Nrf1, high nuclear expression of Nrf2 and low cytoplasmic expression of Keap1 are associated with adverse outcome in this patient group.

see all

Series: Journal of clinical pathology
ISSN: 0021-9746
ISSN-E: 1472-4146
ISSN-L: 0021-9746
Volume: 72
Issue: 4
Pages: 316 - 321
DOI: 10.1136/jclinpath-2018-205584
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: This study was supported by the Finnish Medical Foundation, the Finnish Medical Society Duodecim, the Thelma Mäkikyrö Foundation, Finnish Society for Oncology, Väisänen fund and Terttu Foundation.
Copyright information: © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: