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

• Main Authors: Peroja Pekka, Pasanen Anna, Haapasaari Kirsi-Maria, Jantunen Esa, Soini Ylermi, Turpeenniemi-Hujanen Taina, Bloigu Risto, Lilja Laura, Kuittinen Outi, Karihtala Peeter
• Format: Article
• Language: English
• Published: BMC 2012-03-01
• Series: Experimental Hematology & Oncology
• Subjects: Antioxidant enzyme; Nitrotyrosine; Prognosis; Reactive oxygen species; Thioredoxin
• Online Access: http://www.ehoonline.org/content/1/1/2

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>The redox state-regulating enzymes GCL and Trx are promising markers in the evaluation of DLBCL prognosis in the era of modern immunochemotherapy.</p>