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
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
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.