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Assessment of the Transcriptional Activity of p53 Improves the Prediction of Recurrence in Superficial Transitional Cell Carcinoma of the Bladder
- Source :
- Clinical Cancer Research. 11:4724-4732
- Publication Year :
- 2005
- Publisher :
- American Association for Cancer Research (AACR), 2005.
-
Abstract
- Purpose: To investigate the value of p53 functional analysis of separated alleles in yeast (FASAY) as a witness of p53/p21 pathway alteration and as a predictor of recurrence in superficial transitional cell carcinomas.Experimental Design: p53 transcriptional activity was prospectively analyzed in 52 newly diagnosed transitional cell carcinoma using FASAY competent for the transactivation of p21 and bax promoters. TP53 and p21 gene expression was quantified by real-time PCR, and expression of corresponding proteins was assessed by immunohistochemistry. In addition to tumor stage and grade, the predictive value of FASAY, real-time PCR, and immunohistochemistry for tumor recurrence was assessed by Cox survival analysis.Results: A total (p21 and bax) or partial (bax only) loss of transcriptional activity was observed in 15 of 52 (29%) and 4 of 52 (7.7%) cases, respectively, a partial loss being consistently associated with R283H mutation. p53 nuclear overexpression grossly overestimated (∼40%) or underestimated (∼10%) the true incidence of p53 transcriptional abnormalities, especially in Ta-T1 grade 1 to 2 tumors. Loss of p21 transactivation significantly correlated with decreased p21 gene expression and lack of expression of p21 (P = 0.001). FASAY had a better predictive value for recurrence than p53 immunohistochemistry (Cox hazard ratio, 6.57 versus 3.95; P = 0.0002 versus 0.019, respectively), whereas neither p21 immunohistochemistry (hazard ratio, 1.9; P = 0.29) nor TP53 or p21 gene expression were significant predictors of recurrence. The prognostic difference between FASAY and p53 immunohistochemistry was maintained in the subgroup of Ta-T1 grade 3 tumors.Conclusions: FASAY is a valuable surrogate marker for assessing p53/p21 pathway alteration and predicts transitional cell carcinoma recurrence better than p53 immunohistochemistry.
- Subjects :
- Adult
Male
Cancer Research
Transcription, Genetic
Tumor suppressor gene
Saccharomyces cerevisiae
Biology
Polymerase Chain Reaction
Transactivation
Predictive Value of Tests
Gene expression
medicine
Humans
Alleles
Survival analysis
Aged
Neoplasm Staging
Aged, 80 and over
Carcinoma, Transitional Cell
Hazard ratio
Middle Aged
Prognosis
medicine.disease
Immunohistochemistry
Survival Analysis
Transitional cell carcinoma
Urinary Bladder Neoplasms
Oncology
Predictive value of tests
Mutation
Cancer research
Female
Neoplasm Recurrence, Local
Tumor Suppressor Protein p53
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....0f7caead6a8eab85b14d85fa2b4fb670