Factores pronósticos moleculares en cáncer de vejiga
SUMMARY: The first study, published in Eur J Cancer 2000; 36:357-362, assessed the prognostic effect of the expression of E-cadherin, beta-catenin and CD44 adhesion molecules in bladder carcinoma. Samples from 40 patients with bladder cancer were studied by immunohistochemistry. The median follow-up was 24 months. Loss of E-cadherin and beta-catenin immunoreactivity was associated with invasiveness, high-grade and p53 over-expression. There was no correlation between CD44 variant expression and outcome. Loss of E-cadherin expression was predictor of poor survival in the multivariable analysis, when assessed with age, grade, stage, and p53 status. When expression of E-cadherin and beta-catenin were evaluated simultaneously, loss of immunoreactivity of both proteins was a strong and independent predictor of poor survival. The second study, published in Cancer 2004; 100:1859-1867, evaluated the immunohistochemical expression of p53, p21 and pRB as predictors of for organ preservation and survival in patients with bladder cancer treated with a combined modality approach with bladder-sparing intent. Eighty-two patients with localized invasive bladder cancer were included. Treatment consisted of transurethral resection, platinum-based neoadjuvant chemotherapy and according to response, either radiotherapy or radical cystectomy. Median follow-up was 55 months. p53 and p21 positive immunoreactivities were independent predictors of decreased survival with bladder preserved (p=.02; p=.02) and disease-free survival (p=.005; p=.009) in a multivariate analysis adjusting for clinical stage, ureteral obstruction and age. Regarding overall survival, p53 overexpression was associated with poor outcome (p=.03), whereas the association with p21 expression did not reach statistical significance (p=.07). No association between pRB immunoreactivity and outcome was found. When the combined expression of p53 and p21 was assessed, the positive expression of both markers was a strong unfavorable prognostic factor for survival with bladder preserved (p=.006), disease-free survival (p=.003) and overall survival (p=.02). In conclusions, loss of expression of E-cadherin, particularly when associated with loss of beta-catenin, is an unfavorable prognostic marker in bladder cancer. The positive expression of p53 and p21, especially when simultaneously assessed, have independent predictive value for poor bladder preservation and survival in bladder cancer patients treated by combined modality therapy and could be useful in the selection of candidates for bladder preserving approaches.
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Advisor:Germá Lluch, José Ramón; Grañena Batista, Alberto
School:Universitat de Barcelona
Source Type:Master's Thesis
Date of Publication:06/21/2004