Interferon-a2b reduces neo-microvascular density in the 'normal' urothelium adjacent to the tumor after transurethral resection of superficial bladder carcinoma

Abstract

Background: As angiogenesis represents one of the hallmarks of cancer we investigated whether intravesically administered interferon-a (IFN-a2b) reduces neo-angiogenesis in the 'normal' urothelium adjacent to the tumor in patients with superficial bladder carcinoma after complete transurethral resection (TUR) of the tumor.

Patients and methods: In the present study 47 patients after TUR of the tumor were examined. 10 patients (group A) received no further treatment (control group); 37 patients (group B) received intravesical treatment with IFN-a2b. The instillations started within 7 days after TUR, were performed weekly for 2 months, twice a month for the next 4 months, and thereafter monthly for 6 more months. Cold cup biopsies were taken before TUR of the transitional cell carcinoma (TCC): from the tumor (T), near tumor (NT) and from normal epithelium (N). Cold cup biopsies 'near tumor', were also taken during follow-up cystoscopy (C1, C2, and C3) 2, 6, and 12 months after TUR, respectively. Angiogenesis was estimated by counting the microvessels detected with CD31 immunostaining.

Results: Significant differences of microvascular density (MVD) between patients of group A and B appear after TUR (p < 0.005, Kruskal-Wallis and Wilcoxon test). The MVD difference was maximal 6 months after TUR (C2(A)-C2(B), second cystoscopy) and measured at 12.17 microvessels/ mm(2) (26.2%).

Conclusion: Our results show that the intravesical administration of IFN-a2b after TUR significantly decreases the angiogenic potential of the 'healthy' urothelium adjacent to the tumor in patients with TCC. This observation could possibly explain, to a certain extent, the mechanism by which IFN-a2b reduces the recurrence rate of primary TCC.