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

Abstract

Objective To investigate Waf1/Cip1 expression and apoptosis, before and after treatment, in tumour biopsies obtained from patients with super®cial bladder cancer who underwent vinorelbine intravesical therapy. Patients and methods Twenty patients with high-risk super®cial 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 ®rst 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 paraf®n-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 signi®cant differences in the cell proliferation marker Ki-67 in biopsies taken before or after treatment. However, p21 Waf1/Cip1 showed signi®-cantly 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 signi®cantly 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 super®cial bladder tumours, and thus a phase II study is warranted.

Thymidylate synthase was associated with patient prognosis and the response to adjuvant therapy in bladder cancer

“…[24] also reported that the Ki-67 proliferation index was significantly greater in TS-positive tumours than in TS-negative tumours, suggesting that TS-negative tumours might have a low rate of cell proliferation. The TS level has also been shown to correlate with the activity of a cell cycle-regulatory protein (p21), which may also influence responses to chemotherapy in bladder cancer [25,26]. p 53 mutant colorectal cancer also express higher levels of TS mRNA [27].…”

Hsp25 and Hsp70 in rodent tumors treated with doxorubicin and lovastatin

“…Apoptosis was revealed by a modification of the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method, using the ApopTag Plus in situ detection kit (Oncor, Gaithersburg, MD, USA). These modifications have been published elsewhere (Cuello-Carrió n and Ciocca 1999;Bonfil et al 2001).…”

Proliferation Ability of Particulated Juvenile Allograft Cartilage

“…Ki-67 protein is expressed in the G1, G2, S, and M cycles of active cell proliferation, but not in the resting G0 cell phase. Based on this feature, immunostaining of Ki-67 is often used to determine the ability of cell proliferation in a tissue, not only in the eld of tumor cell proliferation, but also the proliferation ability of cartilage [18][19][20][21][22]. This study investigated the expression of proliferation-related antigen Ki-67 in transplanted cartilage, and showed the immunohistochemical positive rate of juvenile cartilage was more than that of adult cartilage.…”