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Int J Clin Exp Pathol 2011;4(3):267-275

Original Article
8-hydroxydeguanosine and nitrotyrosine are prognostic factors in urinary bladder

Ylermi Soini, Kirsi-Maria Haapasaari, Markku H Vaarala, Taina Turpeenniemi-Hujanen, V  Kärjä, Peeter Karihtala

Department of  Clinical Pathology and Forensic Medicine, Institute of Clinical Medicine,School of Medicine, Cancer Center of Eastern Finland,
University of Eastern Finland, Kuopio, Finland;
Department of Pathology, Kuopio University Hospital, Kuopio, Finland;
Department of Pathology, Oulu University Hospital and Oulu University, Oulu, Finland;
Department of Surgery, Oulu University Hospital, PO Box 21, 90029 OYS, Oulu, Finland;
Department of Oncology and Radiotherapy, University of Oulu and Oulu University Hospital, P.O. Box 22, FIN-90029, Oulu University Hospital.

Received January 19, 2011; accepted February 28, 2011; Epub March 2, 2011; published March 31, 2011

Abstract: Oxidative stress markers and peroxiredoxins are connected to cancer. A large set of urinary bladder carcinomas were studied for the
expression of nitrotyrosine and 8-hydroxydeguanosine (8OHdG) , two markers indicating oxidative damage. Serum and urine 8-OHdG were
assessed in a subset of patients. We also analysed immunohistochemically the expression of nrf2, keap1, all six peroxiredoxins (prx) and
thioredoxin (trx) in these tumors. 15% of the cases showed 8OHdG and 36% nitrotyrosine positivity. Expression of nitrotyrosine and 8OHdG
associated with a poor prognosis (p=0.050, p=0.011, respectively). Peroxiredoxin positivity ranged from 39% to 84% lowest expression being
for prx 4 and highest for prx 3. Prx 4 expression associated with a poor prognosis (p=0.025) with high grade(p=0.044) and larger tumors (
p=0.023). Cytoplasmic trx positivity was seen in 91 % and nuclear in 59 % of tumors. Nuclear and cytoplasmic trx associated with each other
(p<0.001), and nuclear trx associated with prx 6 (p=0.001), prx 2 (p<0.001), and prx 5 (p<0.001). 8OHdG associated with nuclear trx positivity
(p=0.002), inversely with prx 1 (p=0.025) and with keap1 (p=0.020). Nuclear nrf2 was associated with nitrotyrosine (p=0.042). The results show
that the amount of oxidative stress in urinary bladder tumors affects the prognosis of the patients. Of antioxidative enzymes, prx4 associated
with an unfavourable prognosis. Selective inhibition of prx4 expression might then be one additional option of treatment of bladder cancer.  

Keywords: Urinary bladder, carcinoma, oxidative stress, peroxiredoxin, nrf2, keap1n

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Address all correspondence to:
Ylermi Soini, MD, PhD
Department of Pathology and Forensic Medicine
Institute of Clinical Medicine, Pathology and Forensic Medicine
School of Medicine, University of Eastern Finland, Cancer Center of Eastern Finland
P.O.Box 1627, FI-70211 Kuopio, Finland