Expression and prognostic evaluation of oxidative stress markers in an immunohistochemical study of B-cell derived lymphomas

Abstract

Although oxidative stress plays an important role in the biology of solid malignant tumors, little is known about oxidative stress in hematological malignancies. In this study, we evaluated the immunohistochemical expression and clinical correlations of oxidative stress markers and several essential antioxidant enzymes in B-cell lymphomas. Paraffin-embedded diagnostic tissue samples from 18 diffuse large B-cell lymphomas (DLBCL), 18 follicular lymphomas (FL), 19 Hodgkin lymphomas (HL), 7 chronic lymphocytic leukemias (CLL), 7 mantle cell lymphomas (MCL) and 7 mucosa-associated lymphoid tissue (MALT) lymphomas, together with samples from 6 reactive lymph nodes were stained for oxidative stress markers 8-hydroxydeoxyguanosine (8-OHdG) and nitrotyrosine and antioxidant enzymes manganese superoxide dismutase (MnSOD), thioredoxin (Trx) and γ-glutamyl cysteine synthetase (γ-GCS). There was increased 8-OHdG reactivity in DLBCL compared to more indolent lymphomas and reactive lymph nodes. Positivity for Trx was most intense in HL. In DLBCL, positivity for 8-OHdG and nitrotyrosine associated with shorter survival (p = 0.032 and p = 0.026, respectively). This study showed increasing expression of oxidative stress markers and antioxidant enzymes in a series of lymph node samples evolving from reactive lymph nodes to indolent and aggressive lymphomas. These markers seem to have strong prognostic value, but this has to be verified in larger studies.

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

“…We have previously carried out thorough evaluation of the expression of oxidative stress markers in different forms of lymphoma. In a recent study [22] we found that high levels of GCL and nitrotyrosine, and also low levels of MnSOD correlated with poor prognosis, but the number of patients with DLBCL in that study was only 18. The aim of the present study was to assess the relationships between antioxidant enzymes, oxidative stress markers and prognosis in cases of diffuse large B-cell lymphoma treated in the rituximab era.…”

“…Intensities were discovered to be better suited to assess survival estimates. Staining patterns were discovered and analyzed in our previous study [22]. The staining intensity of cytoplasmic 8-OHdG correlated with high Trx (p = 0.011) and GCL (p = 0.0003) intensities.…”

“…We have previously characterized the expression of the used antibodies in several malignant and pre-malignant tissues [18,19,22,35,36]. Sample evaluation in lymphomas has also been described earlier [22].…”

Oxidative stress markers and mitochondrial antioxidant enzyme expression are increased in aggressive Hodgkin lymphomas

“…Moreover, radiotherapy and chemotherapeutic agents (such as ABVD) used in the treatment of Hodgkin lymphoma are largely based on ROS generation. There is also emerging evidence for other B‐cell malignancies that the malignant B cells are under metabolic oxidative stress and may have altered antioxidant enzyme expression …”

High intensity of cytoplasmic peroxiredoxin VI expression is associated with adverse outcome in diffuse large B-cell lymphoma independently of International Prognostic Index

“…Immunostaining was performed as described previously,16 with a few modifications. The glass slides were incubated in 1.5% H 2 O 2 solution instead of 3% H 2 O 2 , and they were washed with Tris-buffered saline instead of phosphate buffered saline between the different steps of staining.…”