p53 gene and protein status: The role of p53 alterations in predicting outcome in patients with bladder cancer

Ben George, Ram Datar, Lin Wu, Jie Cai, Nancy Patten, Stephen J. Beil, Susan Groshen, John Stein, Donald Skinner, Peter A. Jones, Richard J Cote

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Purpose: The p53 gene status (mutation) and protein alterations (nuclear accumulation detectable by immunohistochemistry; p53 protein status) are associated with bladder cancer progression. Substantial discordance is documented between the p53 protein and gene status, yet no studies have examined the relationship between the gene-protein status and clinical outcome. This study evaluated the clinical relationship of the p53 gene and protein statuses. Materials and Methods: The complete coding region of the p53 gene was queried using DNA from paraffin-embedded tissues and employing a p53 gene-sequencing chip. We compared p53 gene status, mutation site, and protein status with time to recurrence. Results: The p53 gene and protein statuses show significant concordance, yet 35% of cases showed discordance. Exon 5 mutations demonstrated a wild-type protein status in 18 of 22 samples. Both the p53 gene and protein statuses were significantly associated with stage and clinical outcome. Specific mutation sites were associated with clinical outcome; tumors with exon 5 mutations showed the same outcome as those with the wild-type gene. Combining the p53 gene and protein statuses stratifies patients into three distinct groups, based on recurrence-free intervals: patients showing the best outcome (wild-type gene and unaltered protein), an intermediate outcome (either a mutated gene or an altered protein) and the worst outcome (a mutated gene and an altered protein). Conclusion: We show that evaluation of both the p53 gene and protein statuses provides information in assessing the clinical recurrence risk in bladder cancer and that the specific mutation site may be important in assessing recurrence risk. These findings may substantially impact the assessment of p53 alterations and the management of bladder cancer.

Original languageEnglish
Pages (from-to)5352-5358
Number of pages7
JournalJournal of Clinical Oncology
Volume25
Issue number34
DOIs
StatePublished - Dec 1 2007
Externally publishedYes

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p53 Genes
Urinary Bladder Neoplasms
Proteins
Mutation
Recurrence
Exons
bcl-Associated Death Protein
Nuclear Proteins
Oligonucleotide Array Sequence Analysis
Paraffin
Genes
Immunohistochemistry

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

p53 gene and protein status : The role of p53 alterations in predicting outcome in patients with bladder cancer. / George, Ben; Datar, Ram; Wu, Lin; Cai, Jie; Patten, Nancy; Beil, Stephen J.; Groshen, Susan; Stein, John; Skinner, Donald; Jones, Peter A.; Cote, Richard J.

In: Journal of Clinical Oncology, Vol. 25, No. 34, 01.12.2007, p. 5352-5358.

Research output: Contribution to journalArticle

George, B, Datar, R, Wu, L, Cai, J, Patten, N, Beil, SJ, Groshen, S, Stein, J, Skinner, D, Jones, PA & Cote, RJ 2007, 'p53 gene and protein status: The role of p53 alterations in predicting outcome in patients with bladder cancer', Journal of Clinical Oncology, vol. 25, no. 34, pp. 5352-5358. https://doi.org/10.1200/JCO.2006.10.4125
George, Ben ; Datar, Ram ; Wu, Lin ; Cai, Jie ; Patten, Nancy ; Beil, Stephen J. ; Groshen, Susan ; Stein, John ; Skinner, Donald ; Jones, Peter A. ; Cote, Richard J. / p53 gene and protein status : The role of p53 alterations in predicting outcome in patients with bladder cancer. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 34. pp. 5352-5358.
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AU - Patten, Nancy

AU - Beil, Stephen J.

AU - Groshen, Susan

AU - Stein, John

AU - Skinner, Donald

AU - Jones, Peter A.

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AB - Purpose: The p53 gene status (mutation) and protein alterations (nuclear accumulation detectable by immunohistochemistry; p53 protein status) are associated with bladder cancer progression. Substantial discordance is documented between the p53 protein and gene status, yet no studies have examined the relationship between the gene-protein status and clinical outcome. This study evaluated the clinical relationship of the p53 gene and protein statuses. Materials and Methods: The complete coding region of the p53 gene was queried using DNA from paraffin-embedded tissues and employing a p53 gene-sequencing chip. We compared p53 gene status, mutation site, and protein status with time to recurrence. Results: The p53 gene and protein statuses show significant concordance, yet 35% of cases showed discordance. Exon 5 mutations demonstrated a wild-type protein status in 18 of 22 samples. Both the p53 gene and protein statuses were significantly associated with stage and clinical outcome. Specific mutation sites were associated with clinical outcome; tumors with exon 5 mutations showed the same outcome as those with the wild-type gene. Combining the p53 gene and protein statuses stratifies patients into three distinct groups, based on recurrence-free intervals: patients showing the best outcome (wild-type gene and unaltered protein), an intermediate outcome (either a mutated gene or an altered protein) and the worst outcome (a mutated gene and an altered protein). Conclusion: We show that evaluation of both the p53 gene and protein statuses provides information in assessing the clinical recurrence risk in bladder cancer and that the specific mutation site may be important in assessing recurrence risk. These findings may substantially impact the assessment of p53 alterations and the management of bladder cancer.

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