Cancer · 2004
p53 and p21 Expression levels predict organ preservation and survival in invasive bladder carcinoma treated with a combined-modality approach.
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Garcia del Muro Xavier, Condom Enric, Vigués Francesc, Castellsagué Xavier, Figueras Agnès, Muñoz Josep, Solá Judit, Soler Teresa, Capellà Gabriel, Germà Josep R
Аннотация
BACKGROUND: The purpose of the current study was to evaluate the expression levels of p53, p21 and pRB as predictors of for long-term organ preservation and survival in patients with bladder carcinoma who were treated with bladder-sparing intent using a combined-modality approach.
METHODS: Tumor samples from 82 consecutive patients with localized invasive bladder carcinoma treated on 3 different bladder-sparing studies were examined for p53, p21, and pRB expression by immunohistochemical methods. Treatment consisted of transurethral resection, platinum-based neoadjuvant chemotherapy, and, according to response, either radiotherapy or radical cystectomy. The median follow-up duration was 55 months.
RESULTS: Positive immunoreactivity for p53, p21, and pRB was observed in 47%, 52%, and 67% of patients, respectively. Positive p53 immunoreactivity and positive p21 immunoreactivity were independent predictors of decreased survival with bladder preservation (P = 0.02 and P = 0.02, respectively) and disease-free survival (DFS; P = 0.005 and P = 0.009, respectively) in a multivariate analysis adjusting for clinical stage, ureteral obstruction, and age. Regarding overall survival (OS), p53 overexpression was associated with poor outcome (P = 0.03), whereas the association of poor outcome with p21 expression did not reach statistical significance (P = 0.07). 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 and unfavorable prognostic factor for survival with bladder preservation (P = 0.006), DFS (P = 0.003), and OS (P = 0.02).
CONCLUSIONS: Expression levels of p53 and p21, especially when simultaneously assessed, exhibit independent predictive value for long-term bladder preservation and survival in patients with bladder carcinoma treated with combined-modality therapy. These determinations could be useful in the selection of candidates for bladder-preserving treatment.
METHODS: Tumor samples from 82 consecutive patients with localized invasive bladder carcinoma treated on 3 different bladder-sparing studies were examined for p53, p21, and pRB expression by immunohistochemical methods. Treatment consisted of transurethral resection, platinum-based neoadjuvant chemotherapy, and, according to response, either radiotherapy or radical cystectomy. The median follow-up duration was 55 months.
RESULTS: Positive immunoreactivity for p53, p21, and pRB was observed in 47%, 52%, and 67% of patients, respectively. Positive p53 immunoreactivity and positive p21 immunoreactivity were independent predictors of decreased survival with bladder preservation (P = 0.02 and P = 0.02, respectively) and disease-free survival (DFS; P = 0.005 and P = 0.009, respectively) in a multivariate analysis adjusting for clinical stage, ureteral obstruction, and age. Regarding overall survival (OS), p53 overexpression was associated with poor outcome (P = 0.03), whereas the association of poor outcome with p21 expression did not reach statistical significance (P = 0.07). 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 and unfavorable prognostic factor for survival with bladder preservation (P = 0.006), DFS (P = 0.003), and OS (P = 0.02).
CONCLUSIONS: Expression levels of p53 and p21, especially when simultaneously assessed, exhibit independent predictive value for long-term bladder preservation and survival in patients with bladder carcinoma treated with combined-modality therapy. These determinations could be useful in the selection of candidates for bladder-preserving treatment.
Предметные рубрики MeSH
AdultAgedBiomarkers, TumorBiopsy, NeedleCarcinoma, Transitional CellChemotherapy, AdjuvantCombined Modality TherapyCyclin-Dependent Kinase Inhibitor p21CyclinsFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedNeoplasm InvasivenessNeoplasm StagingPredictive Value of TestsProbabilityPrognosisProportional Hazards ModelsRadiotherapy, AdjuvantRetrospective StudiesRisk AssessmentSurvival AnalysisTransurethral Resection of ProstateTreatment OutcomeTumor Suppressor Protein p53Urinary Bladder Neoplasms