The Gleason Score at 40: Still Making the Grade
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."