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Oxidative stress and redox state-regulating enzymes have prognostic relevance in diffuse large B-cell lymphoma

Pekka Peroja1, Anna Kaisa Pasanen1, Kirsi-Maria Haapasaari2, Esa Jantunen3, Ylermi Soini4, Taina Turpeenniemi-Hujanen1, Risto Bloigu5, Laura Lilja1, Outi Kuittinen1 and Peeter Karihtala1*

Author Affiliations

1 Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, Oulu, Finland

2 Department of Pathology, University of Oulu, Oulu, Finland

3 Institute of Clinical Medicine and Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland

4 Department of Clinical Pathology and Forensic Medicine, School of Medicine, University of Eastern Finland, Cancer Center of Eastern Finland and Kuopio University Hospital, Kuopio, Finland

5 Medical Informatics Group, University of Oulu, Oulu, Finland

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Experimental Hematology & Oncology 2012, 1:2  doi:10.1186/2162-3619-1-2

Published: 26 March 2012

Abstract

Background

Oxidative stress and redox-regulating enzymes may have roles both in lymphomagenesis and resistance to lymphoma therapy. Previous studies from the pre-rituximab era suggest that antioxidant enzyme expression is related to prognosis in diffuse large B-cell lymphoma (DLBCL), although these results cannot be extrapolated to patient populations undergoing modern treatment modalities. In this study we assessed expression of the oxidative stress markers 8-hydroxydeoxyguanosine (8-OHdG) and nitrotyrosine and the antioxidant enzymes thioredoxin (Trx), manganese superoxide dismutase (MnSOD) and glutamate-cysteine ligase (GCL) via immunohistochemistry in 106 patients with DLBCL. All patients were treated with CHOP-like therapy combined with rituximab. Immunostaining results were correlated with progression-free survival, disease-specific survival and traditional prognostic factors of DLBCL.

Results

Strong 8-OHdG immunostaining intensity was associated with extranodal involvement (p = 0.00002), a high International Prognostic Index (p = 0.002) and strong Trx (p = 0.011) and GCL (p = 0.0003) expression. Strong Trx staining intensity was associated with poor progression-free survival (p = 0.046) and poor disease-specific survival (p = 0.015). Strong GCL immunostaining intensity predicted poor progression-free survival (p = 0.049). Patients with either strong Trx or strong nitrotyrosine expression showed significantly poorer progression-free survival (p = 0.003) and disease-specific survival (p = 0.031) compared with the other patients.

Conclusions

The redox state-regulating enzymes GCL and Trx are promising markers in the evaluation of DLBCL prognosis in the era of modern immunochemotherapy.

Keywords:
Antioxidant enzyme; Nitrotyrosine; Prognosis; Reactive oxygen species; Thioredoxin