Oxidative/nitrosative stress and peroxiredoxin 2 are associated with grade and prognosis of human renal carcinoma.
Peroxiredoxins (Prxs) 1-6 were assessed in 138 renal cell carcinomas (RCC) using immunohistochemistry and selected samples by Western blotting analysis. Oxidative/nitrosative damage was evaluated using nitrotyrosine immunoreactivity. The expressions of Prxs were correlated with tumor grade and survival and nitrotyrosine reactivity. Non-malignant kidney tubular cells showed positivity with variable intensity for all six Prxs. In RCCs, most cases were positive for Prxs 1 and 2, while only 15-20% of tumors showed expression for Prxs 3 and 4. Prx 2 was associated with tumors of a lower grade (p=0.009) and with a lower frequency of distant metastases (p=0.046). Patients with tumors expressing Prx2 had better prognosis (p=0.027). Instead, nitrotyrosine was significantly associated with high grade tumors (p=0.001). Compared with the non-malignant kidney tubular cells, low Prx expression in the tumor cells can make them more susceptible to oxidative damage. Prx 2 was more abundantly expressed in low grade tumors, suggesting that this protein could play a role in preventing the development of oxidative damage, which in turn can lead to the activation of pathways leading to 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
Kang
S W
SW
Tammela
T L J
TL
Peltoniemi
M
M
Martikainen
P M
PM
Kinnula
V L
VL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D009392:Nephrectomy; D018384:Oxidative Stress; D010544:Peroxidases / Q000032:analysis / Q000378:metabolism*; D054464:Peroxiredoxins; D011379:Prognosis; D016019:Survival Analysis; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism
D014408:Biomarkers, Tumor; C002744:3-nitrotyrosine; D014443:Tyrosine; D010544:Peroxidases; D054464:Peroxiredoxins