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Alteration in p53/p21 Pathway Strongest Predictor of Bladder Cancer Progression

Altered expression of p53, p21, pRB, and p16 is associated with bladder cancer outcome with p53 being the strongest predictor, followed by p21. This suggests a more pivotal role of the p53/p21 pathway in bladder cancer progression, according to new research.

Combinations of independent, complementary markers may provide a more accurate prediction of outcome compared with a single marker, the researchers note. "For example, patients with p53 wild-type or pRB wild-type tumours have been shown to be at significantly decreased risk of bladder cancer recurrence and mortality compared with patients who have both proteins altered," they write.

To investigate this issue further, Shahrokh F. Shariat, MD, with the Baylor College of Medicine, Houston, Texas, United States, and colleagues conducted immunohistochemical staining of p53, p21, pRB, and p16 on serial sections from archival specimens of 80 patients who underwent bilateral pelvic lymphadenectomy and radical cystectomy for bladder cancer. The median follow-up was 101 months.

The researchers found that p53, p21, and pRB or p16 expression was altered in 56%, 49%, and 54% of tumours, respectively. A total of 83% of patients had at least 1 altered marker while 26% of patients had all 3 altered.

Abnormal expressions of p53, p21, and pRB/p16 expression were each associated with muscle-invasive disease (P = .007, P = .003, and P = .003, respectively), and the alteration of each marker was independently associated with disease progression (P < .038) and disease-specific survival (P < .039).

In addition, the number of altered markers was independently associated with an increased risk of bladder cancer progression (P = .005) and mortality (P = .007).

"The p53 phenotype seems to be the strongest predictor of bladder cancer outcome in patients undergoing radical cystectomy," Dr. Shariat and colleagues conclude.

According to the researchers, the association of the p53/p21 tumour suppressor pathway with bladder cancer outcome was stronger than the association of the pRB/p16 tumour suppressor pathway with bladder cancer outcome. "The mechanisms for these interactions remain to be elucidated," they add.

J Clin Oncol 2004 Feb 23;[Epub ahead of print]. "p53, p21, pRB, and p16 Expression Predict Clinical Outcome in Cystectomy With Bladder Cancer"

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