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


RESULTS
We immunohistochemically assessed expression of peroxiredoxin (Prx) II, Prx III, Prx V, Prx VI, manganese superoxide dismutase (MnSOD), 8-hydroxydeoxyguanosine (8-OHdG) and nitrotyrosine in 99 cases of uniformly treated Hodgkin lymphoma. Localization of 8-OHdG was assessed using transmission electron microscopy, which demonstrated expression in the cytosol and mitochondria. 8-OHdG 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). MnSOD immunostaining in RS cells was related to advanced stage (P = 0.031) and to poorer relapse-free survival (RFS) (P = 0.033). Low 8-OHdG expression in the nuclei of RS cells was a predictor of poorer RFS (P = 0.038). Both 8-OHdG and MnSOD 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.
Department of Oncology and Radiotherapy, Oulu University Hospital and University of Oulu, Oulu, Finland.
Hamid
H
Bur
Kirsi-Maria
KM
Haapasaari
Taina
T
Turpeenniemi-Hujanen
Outi
O
Kuittinen
Päivi
P
Auvinen
Katja
K
Marin
Petri
P
Koivunen
Raija
R
Sormunen
Ylermi
Y
Soini
Peeter
P
Karihtala
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006689:Hodgkin Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D016253:Microscopy, Immunoelectron; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000378:metabolism; D011379:Prognosis; D016539:Reed-Sternberg Cells / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D000975:Antioxidants; D014408:Biomarkers, Tumor; C002744:3-nitrotyrosine; D014443:Tyrosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D054464:Peroxiredoxins; D013482:Superoxide Dismutase; D003849:Deoxyguanosine
8-OHdG; MnSOD; peroxiredoxin; prognosis; reactive oxygen species