P. Kellokumpu-Lehtinen

Prospective Randomized Trial of Interferon Alfa-2a Plus Vinblastine Versus Vinblastine Alone in Patients With Advanced Renal Cell Cancer

PURPOSE The combination of interferon alfa-2a (IFNalpha2a) plus vinblastine (VLB) induces objective tumor responses in patients with advanced renal cell cancer. However, no prospective randomized trial has shown that this treatment prolongs overall survival. We compared overall survival after treatment with IFNalpha2a plus VLB versus VLB alone in patients with advanced renal cell cancer. PATIENTS AND METHODS We prospectively randomized 160 patients with locally advanced or metastatic renal cell cancer to receive either VLB alone or IFNalpha2a plus VLB for 12 months or until progression of disease. In both groups, VLB was administered intravenously at 0.1 mg/kg every 3 weeks, and in the combination group IFNalpha2a was administered subcutaneously at 3 million units three times a week for 1 week, and 18 million units three times a week thereafter for the second and subsequent weeks. For patients unable totolerate IFNalpha2a at 18 million units per injection, the dose was reduced to 9 million units. RESULTS Median survival was 67.6 weeks for the 79 patients receiving IFNalpha2a plus VLB and 37.8 weeks for the 81 patients treated with VLB (P =.0049). Overall response rates were 16. 5% for patients treated with IFNalpha2a plus VLB and 2.5% for patients treated with VLB alone (P =.0025). Treatment with the combination was associated with constitutional symptoms and abnormalities in laboratory parameters, but no toxic deaths were reported. CONCLUSION The combination of IFNalpha2a plus VLB is superior to VLB alone in the treatment of patients with locally advanced or metastatic renal cell carcinoma. This is the first study to demonstrate that survival can be prolonged by using IFNalpha2a for these patients.

Membranous location of EGFR immunostaining is associated with good prognosis in renal cell carcinoma

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=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.

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.

Chromosomal gains and losses detected by comparative genomic hybridization and proliferation activity in renal cell carcinomaDo they give any prognostic information in clinical practice

Objective: The number of DNA losses found using comparative genomic hybridization (CGH) and the proliferation index MIB‐1 have been shown to be prognostic factors in renal cell carcinoma (RCC). We evaluated the associations of these two factors with each other and with histopathology and clinical outcome. Material and Methods: In this prospective study, specimens from 20 primary RCCs were investigated using CGH and MIB‐1 assay. The associations of the commonest chromosomal aberrations with histopathology, stage and the clinical outcome of the disease were evaluated. Results: CGH detected genetic aberrations in all tumours. Losses of genetic material (85%) were more common than gains (65%). Most common was loss in the short arm of chromosome 3, which was found in 70% of the tumours. Other frequent changes (20%) were losses of 4q, 13q, 18 and Xp, as well as gains of 5q, 7p, 7q (25%) and chromosome 12. The number of deleted chromosomal areas varied from none to six. The MIB‐1 index varied from 0 to 39 (median 4.0). The total number of chromosomal aberrations or deletions showed no association with MIB‐1 index or nuclear grade. Most grade 1 and 2 tumours showed a low MIB‐1 index. All nuclear grade 4 tumours progressed and were associated with short survival. Conclusion: CGH gives an overview of DNA changes in RCC and helps to locate targets for more precise genetic evaluation. CGH findings are also helpful for classifying tumours. In this study, genetic aberrations in primary RCCs were not associated with histopathology, proliferation or clinical outcome, which suggests that CGH does not necessarily give any additional information on the prognosis of the disease. MIB‐1 index and TNM stage were associated with survival.