High intensity of cytoplasmic peroxiredoxin VI expression is associated with adverse outcome in diffuse large B-cell lymphoma independently of International Prognostic Index.
OBJECTIVE
Diffuse large B-cell lymphoma (DLBCL) is an aggressive and potentially fatal disease. Prediction of risk of relapse is based on clinical markers. There is a need for more accurate biomarkers to select patients for more aggressive first-line treatments. Peroxiredoxins (Prxs) are a family of potent antioxidant proteins. Their prognostic role in DLBCL is unknown.


METHODS
Altogether, 103 diagnostic biopsy samples from patients with DLBCL were immunohistochemically stained for Prxs I, II, III, V and VI.


RESULTS
Strong Prx VI expression was associated with the presence of B-symptoms. There were no other significant associations with traditional risk factors. Five-year disease-specific survival was 68.6% in patients with high cytoplasmic Prx VI intensity vs 97.0% in those with low intensity. In multivariate analysis, high Prx VI expression (HR 12.846, 95% CI 1.722 to 95.807, p=0.013) was an independent risk factor of lymphoma-associated death not related to International Prognostic Index score (HR 2.514, 95% CI 1.040 to 6.073, p=0.041).


CONCLUSIONS
High intensity of cytoplasmic Prx VI expression in pretreatment DLBCL samples predicts worse outcome in patients with DLBCL. Whether Prx VI is associated with chemoresistance, and therefore a poorer outcome, needs to be evaluated. If Prx VI is a predictive marker and it proves causality, it would be crucial to study Prx VI ability to become a target enzyme for treatment.
Department of Oncology and Radiotherapy, University of Oulu, Medical Research Center and Oulu University Hospital, Oulu, Finland.
Milla Elvi Linnea
ME
Kuusisto
Department of Pathology, University of Oulu and Oulu University Hospital, Oulu, Finland.
Kirsi-Maria
KM
Haapasaari
Department of Oncology and Radiotherapy, University of Oulu, Medical Research Center and Oulu University Hospital, Oulu, Finland.
Taina
T
Turpeenniemi-Hujanen
Department of Internal Medicine, Institute of Clinical Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
Esa
E
Jantunen
Department of Pathology, University of Eastern Finland and Kuopio University Hospital, Cancer Center of Eastern Finland, Kuopio, Finland.
Ylermi
Y
Soini
Department of Oncology and Radiotherapy, University of Oulu, Medical Research Center and Oulu University Hospital, Oulu, Finland.
Pekka
P
Peroja
Medical Informatics and Statistics Research Group, University of Oulu, Oulu, Finland.
Risto
R
Bloigu
Department of Oncology and Radiotherapy, University of Oulu, Medical Research Center and Oulu University Hospital, Oulu, Finland.
Peeter
P
Karihtala
Department of Oncology and Radiotherapy, University of Oulu, Medical Research Center and Oulu University Hospital, Oulu, Finland.
Outi
O
Kuittinen
D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D003593:Cytoplasm / Q000201:enzymology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D054465:Peroxiredoxin VI / Q000032:analysis*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI
IMMUNOHISTOCHEMISTRY; LYMPHOMA; MALIGNANT TUMOURS; MOLECULAR BIOLOGY; TUMOUR MARKERS