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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.

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Epidermal growth factor receptor (EGFR) is a key factor in tumorigenesis. The association between EGFR expression and prognosis in renal cell carcinoma (RCC) is not clear. In our study of 134 RCCs, the cellular location of immunostaining was evaluated and patients with EGFR-positive tumours with prominent membranous staining had a good prognosis. Their overall survival was significantly longer (P ¼ 0.004) than that of patients with either EGFR-negative tumours or with mainly cytoplasmic staining. However, further studies on the different EGFR expression patterns in RCC are needed to clarify their role in the progression of the disease. The epidermal growth factor receptor (EGFR) family has been found to play a central role in tumour progression. Ligand binding to the EGFR, receptor dimerisation and the activation of downstream signalling pathways are molecular events involved in tumorigenesis (Kim and Muller, 1999;Carpenter, 2000. High expression of EGFR is considered to be an unfavourable prognostic factor in patients with a variety of tumours (Lieberman et al, 1985;Slamon et al, 1987;Neal et al, 1990), including renal cell carcinoma (RCC) (Uhlman et al, 1995;Yoshida et al, 1997). However, there are also studies on RCC reporting no association between EGFR and prognosis (Hofmockel et al, 1997). In these studies, in addition to ligand binding and immunohistochemical methods (Yoshida et al, 1997), also Northern blot and Southern blot analyses have been used. In the present study, we examined the association between the location of the EGFR immunostaining and prognosis in RCC. MATERIALS AND METHODS PatientsOur study population consisted of 134 consecutive patients who underwent radical nephrectomy for RCC between 1995 and 1999 at Tampere University Hospital. The median age of the patients (83 men and 51 women) at the time of operation was 64 years (range 35 -86 years). Clinical stage was assigned using the TNM Classification of Malignant Tumours (UICC, 1997). The median follow-up time was 40 months, 49 months for survivors and 12 months for nonsurvivors. During the follow-up time, 40 patients died of RCC and 17 of other causes. SpecimensArchival formalin-fixed, paraffin-embedded RCC material was used for the study. All tissue blocks were re-evaluated (PH), and from a representative area for each tumour a 3-mm core was transferred to a multi-tissue block, which was then used for further analysis. All tumours were classified according to Heidelberg classification (Kovacs et al, 1997) and graded according to the Fuhrman system (Fuhrman et al, 1982) by two pathologists (HH, PM). Immunohistochemical stainingParaffin-embedded multi-tissue blocks were cut 4 -5 mm in thickness and mounted on precoated slides. After deparaffinisation, antigen retrieval was performed by heating the sections in a microwave oven for 2 Â 7 min in 10 mM Tris/1 mM EDTA (pH 9.0) buffer, followed by washes with water. A polyclonal rabbit antiEGFr variant III antibody (Zymed Laboratories, Inc., San Francisco, CA, USA) was used for EGFR immunostai...

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