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

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Author(s): Peroja Pekka | Pasanen Anna | Haapasaari Kirsi-Maria | Jantunen Esa | Soini Ylermi | Turpeenniemi-Hujanen Taina | Bloigu Risto | Lilja Laura | Kuittinen Outi | Karihtala Peeter

Journal: Experimental Hematology & Oncology
ISSN 2162-3619

Volume: 1;
Issue: 1;
Start page: 2;
Date: 2012;
Original page

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

ABSTRACT
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.
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