In recent years, clinicians and researchers have noted that blood
tests made by different companies for the prostate-specific antigen
(PSA) yield different results from identical blood samples. In
addition, physicians often don't know which PSA assay their laboratory
uses. This makes it difficult to track changes in a patient's
PSA level, especially if the lab switches to a different company
or PSA test without notice. These inconsistencies have led to
difficulties in assessing patients, Thomas Stamey, MD, Professor
of Urology at Stanford says.
Stamey and two coworkers, Dr. Zuxiong Chen and graduate student
Anthony Prestigiacomo, have developed a stable and reproducible
assay calibrator to solve this problem. Earlier this year, the
International Federation of Clinical Chemistry recommended Stamey's
calibrator for international investigation, and initiated a working
group, headed by Stamey, to oversee standardization of the 25
different PSA assays in Europe.
Stamey's calibrator is now on the agenda for the December meeting
of the National Committee on Clinical Laboratory Standards, which
will consider standardizing the four PSA assays used in the United
A paper describing the Stanford team's work appears in the September
1995 issue of the journal Clinical Chemistry.
The problem with currently available assays, Stamey says, is that
their calibration is based on the form of PSA in semen, although
the assays are used to measure PSA in blood. Early in this decade,
researchers discovered that the form of PSA in blood is completely
different from its form in semen.
"PSA was meant to be only in the ejaculate, because that's
where its natural function is," said Stamey, who pioneered
development of the PSA blood test for prostate cancer in the late
When a man first ejaculates, the ejaculate is a jelly, Stamey
explained. PSA is the enzyme that liquefies the ejaculate and
frees the sperm. Its function is to break down proteins.
When small amounts of PSA leak naturally into the bloodstream,
or when a cancerous cell totally abandons its normal function
of retaining PSA in the ejaculate, the body recognizes the blood-borne
PSA as an invader, and releases a protein that binds the PSA to
prevent it from breaking down other proteins in the body. So,
to properly calibrate assays for PSA in the bloodstream, Stamey's
team set out to mimic this binding process in the laboratory.
Chen, a senior research associate in urology, figured out how
to take PSA from ejaculate and bind it under laboratory conditions
with the naturally occurring protein that binds it in the bloodstream.
He also purified the resulting protein complex. Then, Prestigiacomo
found that a mixture of 10% PSA in its pure form with 90% PSA
in its bound form would almost exactly mimic the state of PSA
in the blood. He substituted this new calibrator in each of the
four assays approved by the US Food and Drug Administration, and
obtained identical blood PSA readings, effectively solving the
problem of disparate test results. The team then devised a measuring
system for the calibrator that will allow laboratories to use
it as a standard with any of the currently approved PSA assays.
This summer, Stamey's lab began packaging enough of the standardized
preparation to fill 6,000 vials, which Stamey hopes will be used
internationally to recalibrate all assays.
"I believe this is all good news for men over 40 years of
age, in that prostate cancer detection will now be more accurate,
and year-to-year variations caused by switching assays should
not occur," Stamey said.