Prognostic value of p53 in muscle-invasive bladder cancer treated with preoperative radiotherapy

Catherine S. Wu, Alan Pollack, Bogdan Czerniak, Valerian Chyle, Gunar K. Zagars, Colin P N Dinney, Shi Xue Hu, William F. Benedict

Research output: Contribution to journalArticle

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Abstract

Objectives. The relationship of p53 mutations as analyzed immunohistochemically to radiation response and therapeutic outcome was examined in a cohort of 301 patients with muscle-invasive transitional cell carcinoma of the bladder treated relatively uniformly with preoperative radiotherapy (50 Gy in 25 fractions) 4 to 6 weeks prior to radical cystectomy. Methods. Adequate formalin-fixed paraffin-embedded archival tissue for the immunohistochemical staining of p53 using antibody DO1 was obtained in 109 patients. The median follow-up for those living was 91 months. Results. Overall, p53 staining was positive in 56% of the cases, with 60% positive in Stage T2 (n = 48), 42% in Stage T3a (n = 31), and 63% in Stage T3b (n = 30). Overexpression of p53 did not correlate with actuarial local control, distant metastasis freedom, disease freedom, or overall survival. However, significant associations were seen when these analyses were limited to patients with clinical Stage T3b disease. In this subgroup, the actuarial 5-year rates for patients with p53 positively and negatively stained tumors were 55% and 100%, respectively, for distant metastasis freedom (P = 0.01), 51% and 91% for disease freedom (P = 0.04), and 32% and 91% for overall survival (P = 0.006). Cox proportional hazards models that included p53 staining and other prognostic factors of significance in the univariate analyses revealed p53 to be independently predictive of survival for patients with Stage T3b disease. Conclusions. The prognostic value of p53 immunostaining rested with Stage T3b patients. Although no correlations were found with radiation response, p53 positivity in this subgroup was associated with a higher rate of distant metastasis and reduced overall survival. For these patients, p53 negativity would indicate that aggressive local treatment (that is, preoperative radiotherapy and cystectomy) is sufficient, whereas p53 positivity would indicate that multiagent chemotherapy is required because of the increased risk of distant metastasis.

Original languageEnglish
Pages (from-to)305-310
Number of pages6
JournalUrology
Volume47
Issue number3
DOIs
StatePublished - Mar 1 1996
Externally publishedYes

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Urinary Bladder Neoplasms
Radiotherapy
Muscles
Neoplasm Metastasis
Survival
Cystectomy
Staining and Labeling
Radiation
Transitional Cell Carcinoma
Proportional Hazards Models
Paraffin
Formaldehyde
Urinary Bladder
Drug Therapy
Mutation
Antibodies
Therapeutics
Neoplasms

ASJC Scopus subject areas

  • Urology

Cite this

Wu, C. S., Pollack, A., Czerniak, B., Chyle, V., Zagars, G. K., Dinney, C. P. N., ... Benedict, W. F. (1996). Prognostic value of p53 in muscle-invasive bladder cancer treated with preoperative radiotherapy. Urology, 47(3), 305-310. https://doi.org/10.1016/S0090-4295(99)80443-9

Prognostic value of p53 in muscle-invasive bladder cancer treated with preoperative radiotherapy. / Wu, Catherine S.; Pollack, Alan; Czerniak, Bogdan; Chyle, Valerian; Zagars, Gunar K.; Dinney, Colin P N; Hu, Shi Xue; Benedict, William F.

In: Urology, Vol. 47, No. 3, 01.03.1996, p. 305-310.

Research output: Contribution to journalArticle

Wu, CS, Pollack, A, Czerniak, B, Chyle, V, Zagars, GK, Dinney, CPN, Hu, SX & Benedict, WF 1996, 'Prognostic value of p53 in muscle-invasive bladder cancer treated with preoperative radiotherapy', Urology, vol. 47, no. 3, pp. 305-310. https://doi.org/10.1016/S0090-4295(99)80443-9
Wu, Catherine S. ; Pollack, Alan ; Czerniak, Bogdan ; Chyle, Valerian ; Zagars, Gunar K. ; Dinney, Colin P N ; Hu, Shi Xue ; Benedict, William F. / Prognostic value of p53 in muscle-invasive bladder cancer treated with preoperative radiotherapy. In: Urology. 1996 ; Vol. 47, No. 3. pp. 305-310.
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abstract = "Objectives. The relationship of p53 mutations as analyzed immunohistochemically to radiation response and therapeutic outcome was examined in a cohort of 301 patients with muscle-invasive transitional cell carcinoma of the bladder treated relatively uniformly with preoperative radiotherapy (50 Gy in 25 fractions) 4 to 6 weeks prior to radical cystectomy. Methods. Adequate formalin-fixed paraffin-embedded archival tissue for the immunohistochemical staining of p53 using antibody DO1 was obtained in 109 patients. The median follow-up for those living was 91 months. Results. Overall, p53 staining was positive in 56{\%} of the cases, with 60{\%} positive in Stage T2 (n = 48), 42{\%} in Stage T3a (n = 31), and 63{\%} in Stage T3b (n = 30). Overexpression of p53 did not correlate with actuarial local control, distant metastasis freedom, disease freedom, or overall survival. However, significant associations were seen when these analyses were limited to patients with clinical Stage T3b disease. In this subgroup, the actuarial 5-year rates for patients with p53 positively and negatively stained tumors were 55{\%} and 100{\%}, respectively, for distant metastasis freedom (P = 0.01), 51{\%} and 91{\%} for disease freedom (P = 0.04), and 32{\%} and 91{\%} for overall survival (P = 0.006). Cox proportional hazards models that included p53 staining and other prognostic factors of significance in the univariate analyses revealed p53 to be independently predictive of survival for patients with Stage T3b disease. Conclusions. The prognostic value of p53 immunostaining rested with Stage T3b patients. Although no correlations were found with radiation response, p53 positivity in this subgroup was associated with a higher rate of distant metastasis and reduced overall survival. For these patients, p53 negativity would indicate that aggressive local treatment (that is, preoperative radiotherapy and cystectomy) is sufficient, whereas p53 positivity would indicate that multiagent chemotherapy is required because of the increased risk of distant metastasis.",
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T1 - Prognostic value of p53 in muscle-invasive bladder cancer treated with preoperative radiotherapy

AU - Wu, Catherine S.

AU - Pollack, Alan

AU - Czerniak, Bogdan

AU - Chyle, Valerian

AU - Zagars, Gunar K.

AU - Dinney, Colin P N

AU - Hu, Shi Xue

AU - Benedict, William F.

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N2 - Objectives. The relationship of p53 mutations as analyzed immunohistochemically to radiation response and therapeutic outcome was examined in a cohort of 301 patients with muscle-invasive transitional cell carcinoma of the bladder treated relatively uniformly with preoperative radiotherapy (50 Gy in 25 fractions) 4 to 6 weeks prior to radical cystectomy. Methods. Adequate formalin-fixed paraffin-embedded archival tissue for the immunohistochemical staining of p53 using antibody DO1 was obtained in 109 patients. The median follow-up for those living was 91 months. Results. Overall, p53 staining was positive in 56% of the cases, with 60% positive in Stage T2 (n = 48), 42% in Stage T3a (n = 31), and 63% in Stage T3b (n = 30). Overexpression of p53 did not correlate with actuarial local control, distant metastasis freedom, disease freedom, or overall survival. However, significant associations were seen when these analyses were limited to patients with clinical Stage T3b disease. In this subgroup, the actuarial 5-year rates for patients with p53 positively and negatively stained tumors were 55% and 100%, respectively, for distant metastasis freedom (P = 0.01), 51% and 91% for disease freedom (P = 0.04), and 32% and 91% for overall survival (P = 0.006). Cox proportional hazards models that included p53 staining and other prognostic factors of significance in the univariate analyses revealed p53 to be independently predictive of survival for patients with Stage T3b disease. Conclusions. The prognostic value of p53 immunostaining rested with Stage T3b patients. Although no correlations were found with radiation response, p53 positivity in this subgroup was associated with a higher rate of distant metastasis and reduced overall survival. For these patients, p53 negativity would indicate that aggressive local treatment (that is, preoperative radiotherapy and cystectomy) is sufficient, whereas p53 positivity would indicate that multiagent chemotherapy is required because of the increased risk of distant metastasis.

AB - Objectives. The relationship of p53 mutations as analyzed immunohistochemically to radiation response and therapeutic outcome was examined in a cohort of 301 patients with muscle-invasive transitional cell carcinoma of the bladder treated relatively uniformly with preoperative radiotherapy (50 Gy in 25 fractions) 4 to 6 weeks prior to radical cystectomy. Methods. Adequate formalin-fixed paraffin-embedded archival tissue for the immunohistochemical staining of p53 using antibody DO1 was obtained in 109 patients. The median follow-up for those living was 91 months. Results. Overall, p53 staining was positive in 56% of the cases, with 60% positive in Stage T2 (n = 48), 42% in Stage T3a (n = 31), and 63% in Stage T3b (n = 30). Overexpression of p53 did not correlate with actuarial local control, distant metastasis freedom, disease freedom, or overall survival. However, significant associations were seen when these analyses were limited to patients with clinical Stage T3b disease. In this subgroup, the actuarial 5-year rates for patients with p53 positively and negatively stained tumors were 55% and 100%, respectively, for distant metastasis freedom (P = 0.01), 51% and 91% for disease freedom (P = 0.04), and 32% and 91% for overall survival (P = 0.006). Cox proportional hazards models that included p53 staining and other prognostic factors of significance in the univariate analyses revealed p53 to be independently predictive of survival for patients with Stage T3b disease. Conclusions. The prognostic value of p53 immunostaining rested with Stage T3b patients. Although no correlations were found with radiation response, p53 positivity in this subgroup was associated with a higher rate of distant metastasis and reduced overall survival. For these patients, p53 negativity would indicate that aggressive local treatment (that is, preoperative radiotherapy and cystectomy) is sufficient, whereas p53 positivity would indicate that multiagent chemotherapy is required because of the increased risk of distant metastasis.

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