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Molecular Markers for Diagnosis, Staging, and Prognosis of Bladder Cancer

Molecular Markers for Diagnosis, Staging, and Prognosis of Bladder Cancer

Intensive research on the molecular biology of bladder
cancer has provided great insight into the disease over the last decade and is
beginning to shape clinical practice. The article by Williams, Buscarini, and
Stein is a thorough review of biologic markers and the current state of the art
in bladder cancer management. The prolific work from the group at the University
of Southern California (USC) has provided significant insights into cell-cycle
regulatory markers and their role in molecular staging. This group’s solid
basic research and substantial radical cystectomy database serve as worthy
models for translational investigations.

Molecular medicine holds the promise that clinical outcomes will be improved
by directing therapy toward the mechanisms and targets associated with the
growth of an individual patient’s tumor. Translation into clinical practice
has been slow, however. The literature is confusing at times, and the lack of
standardization in areas such as immunohistochemistry limits reproducibility
across clinical labs. Clinicians continue to rely on traditional morphologic and
histologic parameters in order to assess tumor biology and prognosis.

Evaluating New Markers

The case of p53, which is altered in at least one-half of bladder cancers, is
illustrative. A Medline literature search combining the terms "p53"
and "bladder cancer" yields 543 articles published in English. Several
relatively large series with multivariate analyses suggest that alteration of
the p53 pathway provides valuable prognostic information. Nonetheless, evidence
for and against almost every aspect of the role of p53 allows the support of
almost any point of view.

It is also apparent that different abnormalities in p53 may lead to different
clinical outcomes.[1] Translation into clinical practice requires prospective
clinical trials, and a collaborative group from USC, Baylor College of Medicine,
and the University of Chicago have initiated a National Cancer Institute-funded
multicenter, multinational clinical trial to evaluate p53 and other markers in
patients treated with radical cystectomy for cancers pathologically confined to
the muscularis propria or lamina propria. This study will attempt to answer
these questions:

  • Do p53 alterations in bladder-confined transitional cell carcinoma
    significantly increase the risk of recurrence and death?
  • Does adjuvant chemotherapy improve survival in patients with p53
    alterations?

The study will also create a repository of archival tissue for the
examination of other markers (eg, retinoblastoma [Rb] gene) and cell-cycle
regulatory proteins (eg, p16 and p21).

Developing Targeted Therapies

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