DETERMINATION OF INTERFERON-ALPHA RECEPTORS IN UROTHELIAL CANCER AND IN NORMAL UROTHELIUM

Purpose: We determined and compared the presence and frequency of inte rferon-alpha 2b receptors in urothelial neoplasms and normal urotheliu m, since the biological activity of interferons becomes apparent only after they bind to specific receptors. Materials and Methods: With our method detection of interferon-alpha 2b receptors required a large nu mber of cells, that is more than 1 x 10(6) cells per ml. We studied 14 patients with relatively large tumors of all stages and grades. Three patients had grade I, 4 grade II and 7 grade III disease. As controls we used biopsies of normal urothelium from 14 patients who underwent transvesical prostatectomy. Interferon-alpha 2b receptors were detecte d quantitatively through the binding of radiolabeled (125)iodine human recombinant interferon-alpha 2b in normal and malignant urothelial ti ssue samples. The interferon-alpha 2b receptors are expressed as recep tor sites per cell, and the results were evaluated with Scatchard anal ysis. Results: The number of interferon-alpha 2b receptor sites per ce ll ranged from 43 to 100 (mean plus or minus standard deviation 62 +/- 18) in normal urothelium and from 110 to 210 (mean 174 +/- 25) in mal ignant epithelium. This difference was statistically significant (p < 0.001, Student's t test 13.75). The difference in the number of interf eron-alpha 2b receptors in grades I plus II and grade III tumors is su ggestive but not statistically significant (p < 0.10, Student's t test 2.075). High grade tumors expressed greater numbers of interferon-alp ha 2b receptors than low grade tumors. Conclusions: The method used ne eds refining so that it will require fewer cells to determine interfer on-alpha 2b receptors. Interferon-alpha 2b receptors are detected in b ladder urothelium and are abundant in malignant tissue with increasing frequency as tumor grade increases. If we can establish, in the futur e, a correlation of the number of interferon-alpha 2b receptors with t he potential response of patients to intravesical instillation therapy with interferon, we might have an important prognostic method for sel ecting subgroups of patients with transitional cell carcinomas who wil l benefit from interferon-alpha 2b instillation.