Expression of antioxidant enzymes in astrocytic brain tumors.
We studied the expression of antioxidant enzymes (AOEs) and related proteins manganese superoxide dismutase (MnSOD), thioredoxin (Trx), thioredoxin reductase (TrxR), and the catalytic (GLCL-c) and regulatory (GLCL-r) subunits of glutamate cysteine ligase (gamma-glutamylcysteinesynthetase) in 433 astrocytomas. Expression of MnSOD was found in 91%, Trx in 46%, TrxR in 66%, GLCL-c 73% and GLCL-r in 89% of the cases. Diffuse astrocytomas showed more intense staining for Trx (p = 0.002), TrxR (p = 0.004), GLCL-c (p = 0.001), GLCL-r (p = 0.04) and MnSOD (p = 0.01) than pilocytic astrocytomas. Within diffuse astrocytomas only Trx (p = 0.0001) and TrxR (p= 0.04) significantly associated with increased malignancy grade. Necrotic tumors were more often immunopositive for Trx (p = 0.001) and TrxR (p = 0.02) and AOE expression was generally higher in mitotically active tumors. Expression of Trx and lack of MnSOD expression was associated with a worse prognosis in diffuse astrocytomas. None of the AOEs had any prognostic value in pilocytic grade I astrocytomas. Familial astrocytomas, which included 23 of the cases studied, did not differ in their expression of MnSOD from sporadic ones. The results show that MnSOD and Trx may influence the biological behaviour of astrocytomas, possibly by modulating cell proliferation and necrosis in these tumors.
Department of Pathology, Tampere University Hospital, Tampere, Finland.
Hannu
H
Haapasalo
Maarit
M
Kyläniemi
Niina
N
Paunul
Vuokko L
VL
Kinnula
Ylermi
Y
Soini
D000975:Antioxidants / Q000378:metabolism; D001254:Astrocytoma / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D001932:Brain Neoplasms / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D016166:Free Radical Scavengers / Q000378:metabolism; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D010088:Oxidoreductases / Q000378:metabolism*; D011379:Prognosis; D013482:Superoxide Dismutase / Q000235:genetics; D016019:Survival Analysis; D013880:Thioredoxin-Disulfide Reductase / Q000235:genetics; D013879:Thioredoxins / Q000235:genetics; D014018:Tissue Distribution
D000975:Antioxidants; D016166:Free Radical Scavengers; D013879:Thioredoxins; D010088:Oxidoreductases; D013482:Superoxide Dismutase; D013880:Thioredoxin-Disulfide Reductase; D005721:Glutamate-Cysteine Ligase