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Expression of p53 in upper urinary tract urothelial carcinoma

Nature Reviews Urology volume 8, pages 516–522 (2011)Cite this article

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Abstract

The management of upper urinary tract urothelial carcinoma (UUT-UC) is controversial. Radical nephroureterectomy is a major undertaking and has obvious shortcomings in the presence of renal impairment and solitary kidneys, whereas endoscopic management can be associated with a risk of disease progression. There is a pressing need for reliable predictive biomarkers to refine patient selection for renal conservation. p53 is the most frequently investigated molecular marker in UUT-UC. Of the 24 papers published on the subject, expression of p53 is a significant univariate prognostic marker in 12 publications, representing seven unique cohorts. However, multivariate analysis demonstrates that p53 expression is of independent prognostic significance in only five studies, all of which contain potential statistical bias. The currently available data do not, therefore, support a role for p53 in this regard, and suggest a need for prospective large-scale collaborative studies using standardized methods of p53 detection and statistical analysis.

Key Points

  • Management of upper urinary tract urothelial carcinoma (UUT-UC) is controversial—radical ablative surgery is a major undertaking with high associated morbidity, whereas endoscopic management might be associated with disease progression

  • There is a pressing need for molecular pathological staging to aid conventional histopathological assessment of preoperative cytology and biopsy samples

  • The most extensively investigated marker in UUT-UC is p53, a tumor suppressor gene, which is mutated in approximately 50% of human carcinomas

  • Despite consistent data showing that mutant p53 expression is correlated with poor survival, many published trials are statistically flawed

  • p53 expression cannot yet be recommended as an adjunct to standard clinical pathology, and large-scale multicenter trials are urgently needed to determine its independent prognostic value in UUT-UC

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Author information

Authors and Affiliations

  1. Department of Urology, Bristol Royal Infirmary, Upper Maudlin Street, Bristol, BS2 8HW, UK

    Stephen Mitchell

  2. Department of Urology, St. Mary's Hospital at Imperial College Healthcare NHS Trust, Praed Street, London, W2 1NY, UK

    Erik Mayer & Anup Patel

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  1. Stephen Mitchell
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Contributions

S. Mitchell and E. Mayer researched data for the article. S. Mitchell and A. Patel discussed content for the article. S. Mitchell wrote the article, and S. Mitchell and A. Patel reviewed the manuscript before submission.

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Correspondence to Anup Patel.

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Mitchell, S., Mayer, E. & Patel, A. Expression of p53 in upper urinary tract urothelial carcinoma. Nat Rev Urol 8, 516–522 (2011). https://doi.org/10.1038/nrurol.2011.92

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