Getzenberg, left, and Partin. The EPCA-2
test can even tell organ-confined cancer from cancer that has spread
beyond the prostate.
As good as PSA is in detecting prostate cancer,
there's a lot of room for improvement. "Nobody would call PSA
a perfect test," says Robert H. Getzenberg, Ph.D., the Brady's
Research Director, and the Donald S. Coffey Professor of Urology.
For one thing, "PSA is not specific for prostate cancer. It
is often elevated in men with BPH and prostatitis," inflammation
of the prostate. Another flaw: "It tells us that a man has
cancer, but it doesn't tell us much about what kind of cancer we're
dealing with," notes Alan W. Partin, M.D., Ph.D., Director
of Urology. "Is it aggressive? Is it a milder, slower-growing
cancer? These are very important things a man with prostate cancer
would really like to know."
Millions of American
men — more than 25 million, says Getzenberg — are waiting
from biopsy to biopsy, playing a frustrating form of medical roulette,
just looking for an answer: Their PSA test is higher than it should
be, but despite many needle sticks, no cancer has been found on
biopsy. So why isn't the PSA level lower? The idea of cancer growing,
but being repeatedly missed, can be very troubling for these men.
For years, Hopkins researchers have been working to find a better,
more specific "crystal ball" for prostate cancer. Now
a research team, led by Getzenberg, has found one, called EPCA-2
(early prostate cancer antigen-2), that works in a simple blood
The EPCA-2 test involved years of work
and many dedicated scientists, including (Back row): Grant
Cannon, Timothy McMurray, David (Brandy) Yeater. (Middle row) Katherine
Bright, Robert Getzenberg,
Eddy Leman, Elizabeth Dada, Megan Gurganus. (Front row) Simran Jandu,
Their discovery comes after decades
of work by Getzenberg's predecessor, Donald S. Coffey, Ph.D., who
noticed something striking about the nuclei of cancer cells: They're
funny-looking; they're misshapen. Coffey and Getzenberg then characterized
the structural proteins that caused this mess within cancer cells;
they're in a part of the nucleus called the nuclear matrix. One
of these is EPCA-2. In a series of exciting experiments, using a
technique called "focused proteomics," Getzenberg and
colleagues were able to show that EPCA-2 was far more specific than
any other marker identified so far — even PSA — in distinguishing
men with prostate cancer from other men. Further, this test was
able to tell which men had organ-confined cancer, and which men
had cancer that had spread beyond the prostate.
“Our goal has been to try to
identify at the molecular level what the pathologist sees under
the microscope," Getzenberg explains, and so far, EPCA-2 has
performed like a champ. In tests of more than 600 men, "even
in men where PSA has failed, EPCA-2 is almost one hundred percent
specific for prostate cancer, and picks up greater than 90 percent
of the prostate cancer patients." More good news: EPCA-2 does
not appear to be elevated in conditions like BPH and prostatitis.
And, EPCA-2 can detect the presence of prostate cancer in men with
normal PSA levels. EPCA-2 may even be able to distinguish the deadliest
cancers, which quickly develop the ability to spread beyond the
prostate, from those that are less aggressive. More tests are needed,
and EPCA-2 will soon be studied in a large, multicenter trial, with
the goal of obtaining FDA approval for its use.
Many Hopkins scientists were
involved in this groundbreaking work, including Partin; Lori Sokoll
and Daniel Chan, two internationally recognized experts in the development
of cancer biomarkers; and Bruce Trock, a leading epidemiologist
and biostatistician in the field of prostate cancer biomarkers.
Much of the work on this project was carried out by a young investigator
in Getzenberg’s laboratory, Eddy Leman, Ph.D., working with Grant
"These findings are remarkable,
and if they hold up when the marker is tested in a larger group
of prostate cancer patients, they may revolutionize the approach
to screening for prostate cancer," notes Patrick C. Walsh,
M.D. At the very least, adds Partin, "EPCA-2 could help determine
which men with abnormal PSA levels have prostate cancer. But it's
possible that EPCA-2 may even replace PSA one day as the screening
test of choice."