title: Oxidative stress and redox state-regulating enzymes have prognostic relevance in diffuse large B-cell lymphoma.
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.
authors.affiliation: Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Peroja
authors.affiliation: Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Anna Kaisa
authors.initials: AK
authors.lastname: Pasanen
authors.affiliation: Department of Pathology, University of Oulu, Oulu, Finland.
authors.forename: Kirsi-Maria
authors.initials: KM
authors.lastname: Haapasaari
authors.affiliation: Institute of Clinical Medicine and Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Esa
authors.initials: E
authors.lastname: Jantunen
authors.affiliation: 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.
authors.forename: Ylermi
authors.initials: Y
authors.lastname: Soini
authors.affiliation: Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Taina
authors.initials: T
authors.lastname: Turpeenniemi-Hujanen
authors.affiliation: Medical Informatics Group, University of Oulu, Oulu, Finland.
authors.forename: Risto
authors.initials: R
authors.lastname: Bloigu
authors.affiliation: Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Lilja
authors.affiliation: Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Kuittinen
authors.affiliation: Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, Oulu, Finland.
authors.forename: Peeter
authors.initials: P
authors.lastname: Karihtala