Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, Oulu, Finland.
Department of Pathology, University of Oulu, Oulu, Finland.
Exp Hematol Oncol. 2012 Mar 26;1(1):2. doi: 10.1186/2162-3619-1-2.
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.
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.
The redox state-regulating enzymes GCL and Trx are promising markers in the evaluation of DLBCL prognosis in the era of modern immunochemotherapy.
氧化应激和氧化还原调节酶可能在淋巴瘤的发生和对淋巴瘤治疗的耐药中起作用。在前利妥昔单抗时代的研究表明，抗氧化酶的表达与弥漫性大 B 细胞淋巴瘤（DLBCL）的预后有关，尽管这些结果不能外推到接受现代治疗方式的患者群体。在这项研究中，我们通过免疫组织化学评估了 106 例 DLBCL 患者的氧化应激标志物 8-羟基脱氧鸟苷（8-OHdG）和硝基酪氨酸以及抗氧化酶硫氧还蛋白（Trx）、锰超氧化物歧化酶（MnSOD）和谷胱甘肽连接酶（GCL）的表达。所有患者均接受 CHOP 样联合利妥昔单抗治疗。免疫组化结果与无进展生存期、疾病特异性生存期和 DLBCL 的传统预后因素相关。
强 8-OHdG 免疫染色强度与结外受累有关（p = 0.00002）、高国际预后指数（p = 0.002）以及强 Trx（p = 0.011）和 GCL（p = 0.0003）表达有关。强 Trx 染色强度与无进展生存期差有关（p = 0.046）和疾病特异性生存期差有关（p = 0.015）。强 GCL 免疫染色强度预测无进展生存期差（p = 0.049）。与其他患者相比，强 Trx 或强硝基酪氨酸表达的患者无进展生存期（p = 0.003）和疾病特异性生存期（p = 0.031）显著较差。
在现代免疫化疗时代，氧化还原状态调节酶 GCL 和 Trx 是评估 DLBCL 预后的有前途的标志物。
