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
|Author:||Kari, Esa1,2; Teppo, Hanna-Riikka1,3; Haapasaari, Kirsi-Maria3;|
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
|Online Access:||PDF Full Text (PDF, 2.6 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2019070122439
|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.
Journal of clinical pathology
|Pages:||316 - 321|
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
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.
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