Premium
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
Author(s) -
Bonfil R.D.,
Gonzalez A.D.,
Siguelboim D.,
Cuello Carrion F.D.,
Ciocca D.R.,
Villaronga A.,
Metz L.,
Mosso F.,
Fayad E.,
Reale M.,
Schmilovich A.J.
Publication year - 2001
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1046/j.1464-410x.2001.02340.x
Subject(s) - medicine , vinorelbine , immunohistochemistry , tunel assay , urology , pathology , terminal deoxynucleotidyl transferase , biopsy , bladder cancer , apoptosis , chemotherapy , cancer , cisplatin , biochemistry , chemistry
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 cancer (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. Transurethral tumour marker biopsies were obtained one week before the first instillation of the drug and one week after the last. The biopsies were immunostained for Ki‐67 and p21 Waf1/Cip1 with monoclonal antibodies, on tissue sections derived from paraffin‐embedded samples obtained before and after vinorelbine treatments. In addition, apoptosis was determined using a terminal deoxynucleotidyl transferase‐mediated dUTP biotin nick‐end labelling (TUNEL) technique. Results There were no significant differences in the cell proliferation marker Ki‐67 in biopsies taken before or after treatment. However, p21 Waf1/Cip1 showed significantly higher expression in biopsies obtained after vinorelbine treatment, with median (range) values of 40 (20–90)% before and 70 (50–80)% after ( P < 0.001, paired nonparametric Wilcoxon test). The apoptotic index was significantly higher after vinorelbine therapy, with median (range) values of 0.89 (0.06–3.8)% before and 2.25 (0.17–18.7)% after treatment ( P < 0.001, paired nonparametric Wilcoxon test). Despite the brief treatment and few patients there was a clinical response in nine patients, together with low toxicity in all. Conclusion The intravesical treatment of tumours with vinorelbine affects p21 Waf1/Cip1 expression without blocking cell proliferation, although increasing apoptosis. The preliminary results suggest that vinorelbine may be useful for treating superficial bladder tumours, and thus a phase II study is warranted.