Bilharzial related, organ confined, muscle invasive bladder cancer: Prognostic value of apoptosis markers, proliferation markers, p53, E-cadherin, epidermal growth factor receptor and c-erbB-2

Purpose: We investigated the association of the apoptosis related proteins Bcl-2, Bcl-x, Bax and Bak, p53, the adhesion molecule E-cadherin, the recep tor proteins epidermal growth factor receptor and c-erbB-2, and the prolife ration markers proliferating cell nuclear antigen and Ki-67 with the clinic al outcome of bilharzial related transitional cell carcinoma and squamous c ell carcinoma. Materials and Methods: Cystectomy specimens from 109 patients with organ co nfined, muscle invasive stage, pT2pN0M0, bilharziall positive bladder cance r were examined, including 60 with squamous cell carcinoma and 49 with tran sitional cell carcinoma. Immunohistochemical results were correlated with t umor progression. Results: 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, respec tively). On univariate analysis patients with transitional cell carcinoma h ad a poorer prognosis than those with squamous cell carcinoma. p53 Over exp ression and the loss of Bak positivity were associated with shortened progr ession-free survival in transitional cell carcinoma (p = 0.006 and 0.04, re spectively), and squamous cell carcinoma (p = 0.00001 and 0.04, respectivel y). In squamous cell carcinoma high tumor grade (p = 0.02) and in transitio nal 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 w ith a poorer prognosis. On multivariate analysis p53 emerged as a significa nt prognostic factor for each condition. Additional independent prognostic factors were proliferating. cell nuclear antigen for squamous cell carcinom a, and MLB-I, Bcl-x and Bas for transitional cell carcinoma. Conclusions: Bilharzial related transitional cell carcinoma and squamous ce ll carcinoma of the. bladder differ in interims of protein expression and p rognosis. 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.