p53 and p21 Expression levels predict organ preservation and survival in invasive bladder carcinoma treated with a combined-modality approach.
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.
Garcia del Muro
Xavier
X
Department of Medical Oncology, Institut Català d'Oncologia, Barcelona, Spain. garciadelmuro@csub.scs.es
Condom
Enric
E
Vigués
Francesc
F
Castellsagué
Xavier
X
Figueras
Agnès
A
Muñoz
Josep
J
Solá
Judit
J
Soler
Teresa
T
Capellà
Gabriel
G
Germà
Josep R
JR
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000401:mortality* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D020728:Transurethral Resection of Prostate / Q000379:methods; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000628:therapy
D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53