Antioxidant enzymes in renal cell carcinoma.
The aim of the study was to estimate the significance of oxidative/nitrosative damage and expression of antioxidant enzymes in renal cell carcinomas (RCC). For this we investigated immunohistochemically six antioxidant enzymes (AOEs) including MnSOD, ECSOD, thioredoxin, thioredoxin reductase, and gammaglutamyl cysteine synthetase heavy and light chain in 138 RCCs. As an indicator of oxidative/nitrosative damage, sections were stained with an antibody to nitrotyrosine. The extent of apoptosis was evaluated by TUNEL method and proliferation by immunohistochemistry to Ki67. Variable expression of all AOEs could be seen in RCC with expression of MnSOD being strongest. Nitrotyrosine was significantly associated with high grade tumors. MnSOD was associated with tumors of a lower stage. Cases showing ECSOD reactivity had higher and cases expressing thioredoxin lower apoptotic index than other tumors. No association with patient prognosis was observed. According to the results renal cell carcinomas show oxidative/nitrosative damage which, according to nitrotyrosine staining, was higher in high grade tumors. Of AOEs, MnSOD was more abundantly expressed in low stage tumors suggesting that its antioxidant function could play a main role to prevent development of oxidative damage leading to more aggressive tumors.
Soini
Y
Y
Department of Pathology, University of Oulu, Oulu, Finland. msoini@cc.oulu.fi
Kallio
J P
JP
Hirvikoski
P
P
Helin
H
H
Kellokumpu-Lehtinen
P
P
Tammela
T L J
TL
Peltoniemi
M
M
Martikainen
P M
PM
Kinnula
L V
LV
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000032:analysis*; D017209:Apoptosis; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology*; D002374:Catalase / Q000032:analysis; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007680:Kidney Neoplasms / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D013482:Superoxide Dismutase / Q000032:analysis; D013880:Thioredoxin-Disulfide Reductase / Q000032:analysis; D013879:Thioredoxins / Q000032:analysis; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D000975:Antioxidants; C002744:3-nitrotyrosine; D014443:Tyrosine; D013879:Thioredoxins; D002374:Catalase; C441642:SOD3 protein, human; D013482:Superoxide Dismutase; D013880:Thioredoxin-Disulfide Reductase; D005721:Glutamate-Cysteine Ligase