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We investigated the association of the apoptosis related proteins Bcl-2, Bcl-x, Bax and Bak, p53, the adhesion molecule E-cadherin, the receptor proteins epidermal growth factor receptor and c-erbB-2, and the proliferation markers proliferating cell nuclear antigen and Ki-67 with the clinical outcome of bilharzial related transitional cell carcinoma and squamous cell carcinoma.Cystectomy specimens from 109 patients with organ confined, muscle invasive stage, pT2pN0M0, bilharziall positive bladder cancer were examined, including 60 with squamous cell carcinoma and 49 with transitional cell carcinoma. Immunohistochemical results were correlated with tumor progression.In squamous cell carcinoma but not in transitional cell carcinoma the loss of epidermal growth factor receptor, Bax and Bak was significantly associated with higher histological grade (p = 0.02, 0.006 and 0.01, respectively). On univariate analysis patients with transitional cell carcinoma had a poorer prognosis than those with squamous cell carcinoma. p53 Over expression and the loss of Bak positivity were associated with shortened progression-free survival in transitional cell carcinoma (p = 0.006 and 0.04, respectively), and squamous cell carcinoma (p = 0.00001 and 0.04, respectively). In squamous cell carcinoma high tumor grade (p = 0.02) and in transitional cell carcinoma high labeling indexes for MIB-1, Bcl-x expression and c-erbB-2 positivity (p = 0.03, 0.02 and 0.04, respectively) were associated with a poorer prognosis. On multivariate analysis p53 emerged as a significant prognostic factor for each condition. Additional independent prognostic factors were proliferating cell nuclear antigen for squamous cell carcinoma, and MIB-1, Bcl-x and Bax for transitional cell carcinoma.Bilharzial related transitional cell carcinoma and squamous cell carcinoma of the bladder differ in interims of protein expression and prognosis. Independent prognostic factors were p53, MIB-1, Bcl-x, and Bax in the former disease, and p53 and proliferating cell nuclear antigen in the latter disease.

Since squamous cell differs from transitional cell cancer regarding histopathology, clinical outcome and etiology, the underlying genetic effects of these 2 tumor types may also be different. We compared numerical aberrations of chromosomes 7, 9 and 17 in bilharzial squamous cell carcinoma, and bilharzial and nonbilharzial transitional cell carcinoma by fluorescence in situ hybridization, and correlated the findings to p53 positivity of the 3 tumor types.Cystectomy for invasive bladder cancer was performed in 169 men and 51 women with a mean age of 54.8 years (range 28 to 83). Of the 220 patients 100 (45.4%) had histologically verified bilharzial squamous cell carcinoma, 61 (27.7%) bilharzial transitional cell carcinoma and 59 (26.8%) nonbilharzial transitional cell carcinoma. Using fluorescence in situ hybridization cystectomy specimens were evaluated for numerical aberrations of chromosomes 7, 9 and 17, and p53 detection was performed by immunohistochemistry.Aberrations of chromosome 7 were observed in 79% of the bilharzial squamous cell carcinoma specimens, and 100% and 93.2% of bilharzial and nonbilharzial transitional cell carcinoma specimens, respectively (p = 0.00011). Aberrations of chromosome 9 were seen in 92% of squamous cell carcinoma specimens but in only 52.4% and 60.9% of bilharzial and nonbilharzial transitional cell carcinoma, respectively (p0.00001). Aberrations of chromosome 17 were found in only 29% of squamous cell carcinoma specimens, compared to 83.6% and 84.7% aberrations of chromosome 17 in both transitional cell carcinoma groups, respectively (p0.00001). The p53 over expression was similar in all 3 tumor types with 82% for squamous cell carcinoma, and 73.7% for bilharzial and 81.3% for nonbilharzial transitional cell carcinoma (not significant, p = 0.5285).Our data show clear differences between chromosomal patterns of invasive bilharzial squamous cell carcinoma and invasive bilharzial or nonbilharzial transitional cell carcinoma but similar frequencies of p53 over expression in all 3 tumor types. However, aberrations of chromosome 9 were observed in all analyzed groups, which confirms the 2 pathways in the oncogenesis of squamous cell and transitional cell carcinoma at the cytogenetic level as suggested by molecular studies.

Objectives. To evaluate the prognostic value of chromosomal aberrations in muscle invasive bladder cancer, because they are of diagnostic and prognostic significance in superficial bladder cancer. Methods. One hundred ninety patients, who underwent radical cystectomy because of squamous cell carcinoma (SCC) of the urinary bladder in 94 cases and transitional cell carcinoma (TCC) in 96 cases, were studied retrospectively. Numerical aberrations of chromosomes 7, 9, and 17, p53 positivity, histologic stage and grade, histologic tumor type, lymph node status, and the presence of bilharzial eggs were investigated as possible prognostic factors. Results. Univariate analysis demonstrated the prognostic significance of all parameters analyzed, excluding chromosome 9. Multivariate analysis revealed only T category (P = 0.01095266), lymph node involvement (P = 0.00054877), and p53 positivity (P = 0.0316974) to be independent prognostic factors in muscle invasive SCC and TCC. Conclusions. Although chromosomal aberrations are associated with progression-free survival, they are not independent prognostic factors and give the clinician no additional information on patients with muscle invasive bladder cancer.

Objectives. The combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) is currently considered the most effective chemotherapy for metastatic transitional cell cancer (TCC) of the urinary tract, but because of its considerable toxicity, alternative regimens appear very interesting. We evaluated the efficacy and toxicity of a combination of paclitaxel and carboplatin as first-line therapy for metastatic TCC. Methods. Thirty-two patients (8 women, 24 men; mean age 67.03 years, range 50 to 79) with metastatic TCC of the bladder or upper urinary tract were included in the study. Paclitaxel (175 mg/m 2 ) was given as a 3-hour intravenous infusion, carboplatin was dosed to an area under the plasma concentration curve of 5 mg/mL/min calculated according to the Calvert formula [(creatinine clearance + 25) × 5] as a 30-minute intravenous infusion immediately after paclitaxel. Response evaluation was performed after every 2 cycles and additional therapy depended on response. The maximum number of cycles was 6. Results. With a mean follow-up of 13.1 months (range 2 to 28), 23 of 32 patients responded to treatment (response rate 71.9%), with 31.3% complete remission (CR) (10 of 32) and 40.6% partial remission (PR) (13 of 32). Four patients (12.5%) had stable disease, and 5 patients (15.6%) showed progression. These results compare well with the outcome after MVAC. Toxicity was mainly characterized by neurotoxicity grade 3 and 4 in 9.4%, grade 3 and 4 leukopenia in 37.5%, and grade 3 thrombocytopenia in 3.1% of the patients. No nephrotoxicity was observed, but all patients developed alopecia. Time to progression after CR was a mean of 7.0 months (range 4 to 13) and after PR a mean of 5.9 months (range 2 to 9). Conclusions. Paclitaxel/carboplatin is an effective therapy for metastatic TCC, with low toxicity.