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Oxidative stress markers and mitochondrial antioxidant enzyme expression are increased in aggressive Hodgkin lymphomas
Author(s) -
Bur Hamid,
Haapasaari KirsiMaria,
TurpeenniemiHujanen Taina,
Kuittinen Outi,
Auvinen Päivi,
Marin Katja,
Koivunen Petri,
Sormunen Raija,
Soini Ylermi,
Karihtala Peeter
Publication year - 2014
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12389
Subject(s) - oxidative stress , antioxidant , enzyme , mitochondrion , medicine , oxidative phosphorylation , biology , pathology , biochemistry
Aims Hodgkin lymphoma treatments are largely based on the generation of reactive oxygen species, but increased expression of antioxidant enzymes may contribute to chemoresistance. The aims of this study were: to define the extent and prognostic value of oxidative stress marker and antioxidant enzyme expression in Hodgkin lymphomas; and to investigate a potential association between antioxidant enzymes and chemoresistance. Methods and results We immunohistochemically assessed expression of peroxiredoxin (Prx) II , Prx III , Prx V , Prx VI , manganese superoxide dismutase (Mn SOD ), 8‐hydroxydeoxyguanosine (8‐ OH dG) and nitrotyrosine in 99 cases of uniformly treated Hodgkin lymphoma. Localization of 8‐ OH dG was assessed using transmission electron microscopy, which demonstrated expression in the cytosol and mitochondria. 8‐ OH dG expression in Reed–Sternberg ( RS ) cells was associated with advanced stage ( P = 0.006) and a lower International Prognostic Score ( P = 0.004). Prx III expression in reactive cellular infiltrate was associated with advanced stage ( P = 0.002) and B ‐symptoms ( P = 0.0006). Strong cytoplasmic Prx V immunostaining was associated with a low rate of complete response to chemotherapy ( P = 0.043). Mn SOD immunostaining in RS cells was related to advanced stage ( P = 0.031) and to poorer relapse‐free survival ( RFS ) ( P = 0.033). Low 8‐ OH dG expression in the nuclei of RS cells was a predictor of poorer RFS ( P = 0.038). Both 8‐ OH dG and Mn SOD were also significant RFS predictors in multivariate analysis. Conclusions Our results suggest that significant oxidative stress exists in Hodgkin lymphomas, both in RS cells and in reactive cellular infiltrates. Mitochondrial antioxidant enzymes are induced in the most aggressive forms of the disease, and they may play some part in chemoresistance.