| The Gleason scoring
system -- named after the Veterans Administration pathologist who
figured out how to crack the code of prostate cancer's highly complicated
mix of cells--turns 40 this year. Prostate tissue is notoriously
tough to read, and until Donald F. Gleason's innovative formula,
many pathologists were stumped by what they saw under the microscope.
Gleason's breakthrough system defines cancer cells solely by their
architectural pattern; the two most common patterns are added together,
and their sum signals how mild-mannered, or how aggressive, the
cancer will likely turn out to be. "It's a testament to the enduring
power of Gleason's original ideas that this is still the accepted
grading system throughout the world," says Hopkins pathologist Jonathan
Epstein, M.D. Epstein, the Rose-Lee and Keith Reinhard Professor
of Urologic Pathology, is world-renowned himself, for his expertise
and accuracy in judging prostate cells.
Just
about everything in the
field of prostate cancer has
changed dramatically over the last
four decades. What about the
way we grade cancer?
And yet, just about everything else
in the field of prostate cancer has changed dramatically over the
last four decades -- particularly, how the disease is diagnosed.
"In the 1960s, there was no screening for prostate cancer other
than by digital rectal exam," says Epstein. There was no PSA test;
in fact, nobody knew that PSA was even in the bloodstream. Even
in the 1970s, Epstein adds, "the vast majority -- 86 percent --
of men were diagnosed with advanced disease." Eight percent were
diagnosed with a localized spot that could be felt during a rectal
exam, and only 6 percent had a tumor that was too small to be felt
(these were found by transurethral resection, a procedure to treat
benign enlargement of the prostate).
Biopsies were much different then,
too -- maybe two thick-gauge needles, inserted into a suspicious
area of the prostate. Today, urologists use much thinner needles,
and do their best to sample the entire prostate -- routinely taking
a dozen or more cores of tissue. In the 1960s, radical prostatectomy
was relatively uncommon. "Prostates were not as often removed intact,
and glands were not processed in their entirety, or as extensively
and systematically as we do today," Epstein says. The original Gleason
system didn't have to deal with grading multiple nodules within
the same prostate; it also predated the use of special techniques,
such as immunohistochemistry, which can help detect cell changes
that mimic prostate cancer. And Gleason probably didn't see too
much PIN (prostatic intraepithelial neoplasia, "funny-looking" cells
that are likely precancerous), because he didn't get to view much
prostate tissue in the early stages of cancer.
To address these and other issues,
Epstein recently brought together more than 80 urological pathologists
from 16 countries with special expertise in prostate cancer. Among
the many decisions they hammered out, the pathologists dealt with
some practical issues involving how to grade cancer in surgically
removed prostate specimens, in needle biopsies and individual needle
cores; and made modifications in some of the Gleason patterns.
"Our conference brought out many
differences in how the Gleason system is applied -- even within
the United States," reports Epstein. "In all but a few areas, clear
consensus was reached by the majority of genitourinary pathologists
who participated in this meeting. We hope that these guidelines
will help pathologists adapt the Gleason grading system to current
practice in a more uniform manner, while at the same time fostering
collaborative studies to address controversial areas, where we need
more data."
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