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


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%).


CONCLUSIONS
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.
Giannopoulos
A
A
Department of Urology, School of Medicine, University of Athens, Laiko Hospital, Athens, Greece.
Adamakis
I
I
Evangelou
K
K
Giannopoulou
M
M
Zacharatos
P
P
Zsantoulis
P
P
Perunovic
B
B
Athanasiou
A
A
Retalis
G
G
Constandinidis
C
C
Gorgoulis
V G
VG
D000283:Administration, Intravesical; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001706:Biopsy; D002295:Carcinoma, Transitional Cell / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D003558:Cystoscopy; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000517:prevention & control; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D011446:Prospective Studies; D011994:Recombinant Proteins; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D019459:Urothelium / Q000098:blood supply*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins