Immunohistochemical analysis of Ki-67, p21(waf1/cip1) and apoptosis in marker lesions from patients with superficial bladder tumours treated with vinorelbine intravesical therapy in a preliminary phase I trial

Citation
Rd. Bonfil et al., Immunohistochemical analysis of Ki-67, p21(waf1/cip1) and apoptosis in marker lesions from patients with superficial bladder tumours treated with vinorelbine intravesical therapy in a preliminary phase I trial, BJU INT, 88(4), 2001, pp. 425-431
Citations number
25
Categorie Soggetti
Urology & Nephrology
Journal title
BJU INTERNATIONAL
ISSN journal
14644096 → ACNP
Volume
88
Issue
4
Year of publication
2001
Pages
425 - 431
Database
ISI
SICI code
1464-4096(200109)88:4<425:IAOKPA>2.0.ZU;2-F
Abstract
Objective To investigate Ki-67 and p21(Waf1/Cip1) expression and apoptosis, before and after treatment, in tumour biopsies obtained from patients with superficial bladder cancer who underwent vinorelbine intravesical therapy. Patients and methods Twenty patients with high-risk superficial bladder can cer (including one or more of the following parameters: tumour diameter >3 cm, histological grade 3, or multicentric tumours) were treated 1-6 times ( weekly) with intravesical vinorelbine (50 mg/mL) instillations. Transurethr al tumour marker biopsies were obtained one week before the first instillat ion of the drug and one week after the last. The biopsies were immunostaine d for Ki-67 and p21(Waf1/Cip1) with monoclonal antibodies, on tissue sectio ns derived from paraffin-embedded samples obtained before and after vinorel bine treatments. In addition, apoptosis was determined using a terminal deo xynucleotidyl transferase-mediated dUTP biotin nick-end labelling (TUNEL) t echnique. Results There were no significant differences in the cell proliferation mar ker Ki-67 in biopsies taken before or after treatment. However, p21(Waf1/Ci p1) showed significantly higher expression in biopsies obtained after vinor elbine treatment, with median (range) values of 40 (20-90)% before and 70 ( 50-80)% after (P < 0.001, paired nonparametric Wilcoxon test). The apoptoti c index was significantly higher after vinorelbine therapy, with median (ra nge) values of 0.89 (0.06-3.8)%, before and 2.25 (0.17-18.7)% after treatme nt (P < 0.001, paired nonparametric Wilcoxon test). Despite the brief treat ment and few patients there was a clinical response in nine patients, toget her with low toxicity in all. Conclusion The intravesical treatment of tumours with vinorelbine affects p 21(Waf1/Cip1) expression without blocking cell proliferation, although incr easing apoptosis. The preliminary results suggest that vinorelbine may be u seful for treating superficial bladder tumours, and thus a phase II study i s warranted.