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"Molecular Staging" Assessing
The E-Cadherin Gene: When The Loss Of A Gene Can Have Predictive Potential
(November 2006)
The gene, E-Cadherin,
codes for a cell-cell surface adhesion protein involved in the control of
cell migration and invasion. It was mentioned in the first article, so
some elaboration is in order. Its loss from prostatic tissue
has been found to predict a high-risk of metastatic spread, even in
presumably low-risk settings. The analysis for the E-cadherin protein, or
other biomarkers, might be termed "molecular staging" and is an example
how additional refinement and accuracy can be built into our current
predictive algorithms.
An exemplar case in point
is the data reported in J.Urol., Oct. 2006, from the University of
Michigan: "E-Cadherin Protein Expression Predicts Prostate Cancer Salvage
Radiotherapy Outcomes". Twenty-five of 37 prostate specimens showed,
low E-cadherin expression. Quoting liberally from their
results: "At a median clinical follow-up of 40 months univariate analysis
demonstrated that E-cadherin staining was not associated with Gleason
score, extracapsular extension, surgical margin status, pre-prostatectomy
or pre-radiotherapy prostate specific antigen, complete biochemical
response after radiotherapy or adjunctive hormonal therapy, but it was
associated with seminal vesicle invasion. Two year failure-free survival
was 55% in patients with aberrant [low] E-cadherin expression compared
with 92% in patients with normal E-cadherin expression (p=0.02)".
Sophisticated analyses now combine the assessment of biomarkers such as E-cadherin
expression with other recognized predictors of adverse outcome: bcl-2, an
inhibitor of apoptosis; CD44v6, whose overexpression is associated with
malignant transformation and invasion; the proinvasive matrix
metalloproteinases (MMP), which facilitate cell movement through the
extracellular matrix; and the tumor suppressor, p53. Combinations have the
potential of additional predictive leverage, but Judd Moul, MD, has
pointed out the need for a careful evaluation of the reliability of these
bioassays when performed on core biopsies, since data from small samples
may be misleading. The Michigan report cited above relating low E-cadherin
expression with an adverse outcome needs further confirmation to be
confidently used in clinical practice. However, this article's
highlighting of E-cadherin is a heads-up to suggest forthcoming analytic
aids that may have useful clinical application.
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