Peroxiredoxins and antioxidant enzymes in pilocytic astrocytomas.
OBJECTIVE
Peroxiredoxins are antioxidant enzymes (AOEs), which are redox-regulated thiol proteins with potential effects on the growth, invasion and drug resistance of neoplastic cells. In this study, their biology and clinical significance were examined in pilocytic astrocytomas (PAs).


METHODS
The expression of peroxiredoxins (Prx I-VI) was investigated in 105 PAs by the means of immunohistochemistry and compared with the expression of selected other antioxidant enzymes, cell proliferation, angiogenesis, apoptosis, p53, histopathology and patient survival.


RESULTS
Peroxiredoxins were strongly expressed in general suggesting that oxidative damage and consequent defense takes place during the progression of pilocytic astrocytomas. In agreement with this hypothesis, several other AOEs correlated with the degenerative features and angiogenesis possibly associated with reactive oxygen species-derived cellular damage. Moreover, the expression of the AOEs was associated with each other indicating a concurrent activation of the enzymes. With the exception of manganese superoxide dismutase (MnSOD), a strong expression of AOEs was generally associated with higher cell proliferation. Prx VI seemed to have a positive association with a longer recurrence-free interval while other AOEs had no association with patient survival. Many AOEs, such as MnSOD, induce chemo- and radioresistance and are highly elevated in aggressive malignancies. PAs lack this confounding factor, and these tumors are treated only by surgery.


CONCLUSIONS
Taken together, the results of this study on pilocytic astrocytomas suggest that the levels of Prxs and other AOEs and their related thiol proteins are generally strongly expressed in these tumors. At least Prx VI can contribute to tumor behavior which can make it a potential prognostic factor.
Nordfors
K
K
Department of Pathology, Center for Laboratory Medicine, Tampere University Hospital, P.O. Box 2000, 33521 Tampere, Finland. kmenor@utu.fi
Haapasalo
J
J
Helén
P
P
Paetau
A
A
Paljärvi
L
L
Kalimo
H
H
Kinnula
V L
VL
Soini
Y
Y
Haapasalo
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D001254:Astrocytoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology*; D001932:Brain Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010544:Peroxidases / Q000378:metabolism*; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; D011379:Prognosis; D013482:Superoxide Dismutase / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism
D013879:Thioredoxins; D010544:Peroxidases; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; D013482:Superoxide Dismutase; D013880:Thioredoxin-Disulfide Reductase; D005721:Glutamate-Cysteine Ligase