Expression of Ki-67, p53, and p21WAF1/CIP1 proteins and apoptosis in biopsies from patients with superficial bladder tumors treated with vinorelbine intravesical therapy

GONZALEZ A. D.; SIGUELBOIM D.; CUELLO CARRIÓN F. D.; CIOCCA D. R.; VILLARONGA A.; METZ L.; MOSSO F.; REALE M.; SCHMILOVICH A. J.; BONFIL R. D.

San Francisco, CA, USA

Congreso; 91st Annual Meeting of the American Association for Cancer Research; 2000

American Association for Cancer Research

Preclinical studies carried out by us, suggested that the semisynthetic vinca alkaloid Vinorelbine (VNR) could be useful for intravesical treatment of superficial transitional cell carcinoma of the bladder (J. Urol. 156: 517, 1996; J. Urol. 158: 912, 1997). As a first approach to evaluate it, 20 high risk superficial bladder cancer patients (tumor diameter larger than 3 cm, histologic grade 1-3 or multicentric tumors), were treated with 1 to 6 weekly intravesical VNR (50 mg/ml) instillations, followed by transurethral resection. Paraffin-embedded samples obtained before and after VNR treatment, showed no significant difterences in the cell proliferation marker Ki-67 nor in p53 immunostaining. On the contrary, p21WAF1/CIP1 (a downstream effector of p53 pathway of cell control) showed significant higher expression in biopsies obtained after VNR-treatment (median [range]: preVNR= 40 [20-90] vs. postVNR= 7 [50-80]. P = 0.0001, paired nonparametric Wilcoxon test). A higher apoptotic index (as determined by the TUNEL technique) was observed in the post-chemotherapy biopsies. These findings show that intravesical treatment of tumors with VNR affects p21WAF1/CIP1 expression without blocking cell proliferation though increasing apoptosis.