Structural alteration of p53 protein in patients with muscle invasive bladder transitional cell carcinoma

Rabi Tiguert, Fernando J. Bianco, Peter Oskanian, Yiwei Li, David Grignon, David P. Wood, J. Edson Pontes, Fazlul H. Sarkar

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Purpose: Recent data imply that 3-dimensional (D) p53 protein modeling provides more specific information on its function in patients with pancreatic adenocarcinoma. In addition to immunohistochemical and single strand conformational polymorphism analysis, we performed 3-D p53 protein modeling and correlated our results with the disease-free survival of patients with muscle invasive transitional cell carcinoma of the bladder who underwent surgery. Materials and Methods: We identified 43 patients and analyzed p53 status in each by immunohistochemical testing, single strand conformational polymorphism and DNA sequencing with 3-D protein modeling. Median followup was 38 months (range 4 to 92). The results of each analysis were compared and correlated with cancer specific survival. Statistical analysis was performed using the log rank test on Kaplan-Meier survival curves. Results: The population included 30 men and 13 women 35 to 84 years old (median age 65). Nuclear over expression of p53 protein was observed in 26 of the 43 cases (60%). Lymph node involvement did not correlate with p53 over expression. Significantly more patients with lymph node metastasis died of cancer. Median survival in the 26 patients with p53 over expression was 28 months versus 57 in those with negative staining (p = 0.25). Mutation analysis by single strand conformational polymorphism revealed no abnormality in 24 patients (56%) with a median survival of 28 months, whereas we noted abnormal mutational analysis in 19 (44%) with a median survival of 38 months (p = 0.33). Of 19 single strand conformational polymorphism positive cases DNA sequencing showed mutation near the DNA binding site in 10 (53%), mutation away from the site in 6 (32%) and no mutation in 3 (17%). No survival difference was detected in cases with mutation away and near the DNA binding site, respectively (p = 0.69). Conclusions: In this group of patients treated with radical cystectomy for muscle invasive bladder transitional cell carcinoma, analysis of p53 protein and the p53 gene by immunohistochemical testing, single strand conformational polymorphism and mutational analysis did not correlate with cancer specific survival.

Original languageEnglish (US)
Pages (from-to)2155-2160
Number of pages6
JournalJournal of Urology
Volume166
Issue number6
StatePublished - 2001
Externally publishedYes

Fingerprint

Transitional Cell Carcinoma
Urinary Bladder
Muscles
Survival
Mutation
Proteins
DNA Sequence Analysis
Lymph Nodes
Binding Sites
Negative Staining
Neoplasms
Cystectomy
DNA
p53 Genes
Kaplan-Meier Estimate
Disease-Free Survival
Adenocarcinoma
Neoplasm Metastasis
Population

Keywords

  • Bladder
  • Carcinoma
  • Genes
  • p53
  • Protein p53
  • Survival
  • Transitional cell

ASJC Scopus subject areas

  • Urology

Cite this

Tiguert, R., Bianco, F. J., Oskanian, P., Li, Y., Grignon, D., Wood, D. P., ... Sarkar, F. H. (2001). Structural alteration of p53 protein in patients with muscle invasive bladder transitional cell carcinoma. Journal of Urology, 166(6), 2155-2160.

Structural alteration of p53 protein in patients with muscle invasive bladder transitional cell carcinoma. / Tiguert, Rabi; Bianco, Fernando J.; Oskanian, Peter; Li, Yiwei; Grignon, David; Wood, David P.; Pontes, J. Edson; Sarkar, Fazlul H.

In: Journal of Urology, Vol. 166, No. 6, 2001, p. 2155-2160.

Research output: Contribution to journalArticle

Tiguert, R, Bianco, FJ, Oskanian, P, Li, Y, Grignon, D, Wood, DP, Pontes, JE & Sarkar, FH 2001, 'Structural alteration of p53 protein in patients with muscle invasive bladder transitional cell carcinoma', Journal of Urology, vol. 166, no. 6, pp. 2155-2160.
Tiguert, Rabi ; Bianco, Fernando J. ; Oskanian, Peter ; Li, Yiwei ; Grignon, David ; Wood, David P. ; Pontes, J. Edson ; Sarkar, Fazlul H. / Structural alteration of p53 protein in patients with muscle invasive bladder transitional cell carcinoma. In: Journal of Urology. 2001 ; Vol. 166, No. 6. pp. 2155-2160.
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abstract = "Purpose: Recent data imply that 3-dimensional (D) p53 protein modeling provides more specific information on its function in patients with pancreatic adenocarcinoma. In addition to immunohistochemical and single strand conformational polymorphism analysis, we performed 3-D p53 protein modeling and correlated our results with the disease-free survival of patients with muscle invasive transitional cell carcinoma of the bladder who underwent surgery. Materials and Methods: We identified 43 patients and analyzed p53 status in each by immunohistochemical testing, single strand conformational polymorphism and DNA sequencing with 3-D protein modeling. Median followup was 38 months (range 4 to 92). The results of each analysis were compared and correlated with cancer specific survival. Statistical analysis was performed using the log rank test on Kaplan-Meier survival curves. Results: The population included 30 men and 13 women 35 to 84 years old (median age 65). Nuclear over expression of p53 protein was observed in 26 of the 43 cases (60{\%}). Lymph node involvement did not correlate with p53 over expression. Significantly more patients with lymph node metastasis died of cancer. Median survival in the 26 patients with p53 over expression was 28 months versus 57 in those with negative staining (p = 0.25). Mutation analysis by single strand conformational polymorphism revealed no abnormality in 24 patients (56{\%}) with a median survival of 28 months, whereas we noted abnormal mutational analysis in 19 (44{\%}) with a median survival of 38 months (p = 0.33). Of 19 single strand conformational polymorphism positive cases DNA sequencing showed mutation near the DNA binding site in 10 (53{\%}), mutation away from the site in 6 (32{\%}) and no mutation in 3 (17{\%}). No survival difference was detected in cases with mutation away and near the DNA binding site, respectively (p = 0.69). Conclusions: In this group of patients treated with radical cystectomy for muscle invasive bladder transitional cell carcinoma, analysis of p53 protein and the p53 gene by immunohistochemical testing, single strand conformational polymorphism and mutational analysis did not correlate with cancer specific survival.",
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T1 - Structural alteration of p53 protein in patients with muscle invasive bladder transitional cell carcinoma

AU - Tiguert, Rabi

AU - Bianco, Fernando J.

AU - Oskanian, Peter

AU - Li, Yiwei

AU - Grignon, David

AU - Wood, David P.

AU - Pontes, J. Edson

AU - Sarkar, Fazlul H.

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N2 - Purpose: Recent data imply that 3-dimensional (D) p53 protein modeling provides more specific information on its function in patients with pancreatic adenocarcinoma. In addition to immunohistochemical and single strand conformational polymorphism analysis, we performed 3-D p53 protein modeling and correlated our results with the disease-free survival of patients with muscle invasive transitional cell carcinoma of the bladder who underwent surgery. Materials and Methods: We identified 43 patients and analyzed p53 status in each by immunohistochemical testing, single strand conformational polymorphism and DNA sequencing with 3-D protein modeling. Median followup was 38 months (range 4 to 92). The results of each analysis were compared and correlated with cancer specific survival. Statistical analysis was performed using the log rank test on Kaplan-Meier survival curves. Results: The population included 30 men and 13 women 35 to 84 years old (median age 65). Nuclear over expression of p53 protein was observed in 26 of the 43 cases (60%). Lymph node involvement did not correlate with p53 over expression. Significantly more patients with lymph node metastasis died of cancer. Median survival in the 26 patients with p53 over expression was 28 months versus 57 in those with negative staining (p = 0.25). Mutation analysis by single strand conformational polymorphism revealed no abnormality in 24 patients (56%) with a median survival of 28 months, whereas we noted abnormal mutational analysis in 19 (44%) with a median survival of 38 months (p = 0.33). Of 19 single strand conformational polymorphism positive cases DNA sequencing showed mutation near the DNA binding site in 10 (53%), mutation away from the site in 6 (32%) and no mutation in 3 (17%). No survival difference was detected in cases with mutation away and near the DNA binding site, respectively (p = 0.69). Conclusions: In this group of patients treated with radical cystectomy for muscle invasive bladder transitional cell carcinoma, analysis of p53 protein and the p53 gene by immunohistochemical testing, single strand conformational polymorphism and mutational analysis did not correlate with cancer specific survival.

AB - Purpose: Recent data imply that 3-dimensional (D) p53 protein modeling provides more specific information on its function in patients with pancreatic adenocarcinoma. In addition to immunohistochemical and single strand conformational polymorphism analysis, we performed 3-D p53 protein modeling and correlated our results with the disease-free survival of patients with muscle invasive transitional cell carcinoma of the bladder who underwent surgery. Materials and Methods: We identified 43 patients and analyzed p53 status in each by immunohistochemical testing, single strand conformational polymorphism and DNA sequencing with 3-D protein modeling. Median followup was 38 months (range 4 to 92). The results of each analysis were compared and correlated with cancer specific survival. Statistical analysis was performed using the log rank test on Kaplan-Meier survival curves. Results: The population included 30 men and 13 women 35 to 84 years old (median age 65). Nuclear over expression of p53 protein was observed in 26 of the 43 cases (60%). Lymph node involvement did not correlate with p53 over expression. Significantly more patients with lymph node metastasis died of cancer. Median survival in the 26 patients with p53 over expression was 28 months versus 57 in those with negative staining (p = 0.25). Mutation analysis by single strand conformational polymorphism revealed no abnormality in 24 patients (56%) with a median survival of 28 months, whereas we noted abnormal mutational analysis in 19 (44%) with a median survival of 38 months (p = 0.33). Of 19 single strand conformational polymorphism positive cases DNA sequencing showed mutation near the DNA binding site in 10 (53%), mutation away from the site in 6 (32%) and no mutation in 3 (17%). No survival difference was detected in cases with mutation away and near the DNA binding site, respectively (p = 0.69). Conclusions: In this group of patients treated with radical cystectomy for muscle invasive bladder transitional cell carcinoma, analysis of p53 protein and the p53 gene by immunohistochemical testing, single strand conformational polymorphism and mutational analysis did not correlate with cancer specific survival.

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