The Amazing Gleason Score

BY MARK SCHOLZ, MD


Everyone is excited about the latest craze in medical technology—genetic analysis of tumor cells, which I’ll call GAT for short. The scientific progress that has been made with GAT in my opinion is the second most exciting area of advancement in medical technology today (see further below for more about the first most exciting area). GAT technology is already being commercialized for use in the medical marketplace in products like Prolaris and Oncotype. This technology is able to predict the aggressiveness of prostate cancers, enabling us to differentiate between the men who need immediate treatment and those who can postpone treatment safely.

The predictive power of GAT is certainly exciting, but there is already an effective form of genetic testing available that has been around for more than 40 years, the Gleason scoring system. The Gleason system relies on the visual appearance of cells under the microscope to draw conclusions about their inner genetic makeup. In the medical world, using the visual appearance of the cancer cells is called phenotypic analysis. GAT is genotypic analysis.  Drawing conclusions about underlying genetic makeup by simple visual assessment is a pervasive in human experience.  In courtship, we rely on phenotypic analysis of the underlying genetic make-up of potential spouses to form an opinion about their suitability as potential mates.  Perusal of the genetic pool of immediate family members provides further insight.

So how can Gleason score draw conclusions about the underlying genetic potential for tumor aggressiveness simply by looking at the appearance of cells under a microscope?  The answer is to do a comparison of the visual appearance of cancer cells with the appearance of normal prostate cells. Normal cells in the prostate perform varied functions but still work together as a team.  Specifically, healthy cells form into definable structures called glands.  In these glands some cells manufacture prostatic fluid, a complex liquid comprising the ejaculate for the sperm to swim in.  Other cells organize to form ducts, a piping system to drain the fluid from the outer periphery of the gland and channel it into the middle of the prostate so that a large quantity of fluid can be expelled through the urethra at just the right moment.  All of these different cells work as a team and coexist in the prostate functioning together in a structured glandular arrangement.   
 
When a trained pathologist looks at tumor cells under the microscope he grades them by the degree of cellular disorder.  He is asking himself the question, “How much do these cells retain the normal glandular characteristics of the prostate gland?”  If a cross section of the tumor looks like an unbroken sheet of uniform cells, the cancer is high-grade; the cells have lost their ability to cooperate with each other and form glands. The cancer cells have been honed down into little race cars with only one mission, to aggressively pursue its own replicative destiny. When tumors have this appearance they are graded as a Gleason 9 or 10.  On the other hand, if the appearance of the tumor shows residual glandular components, it is less aggressive, perhaps a Gleason 7.  Gleason 6 “cancer,” the type the one that never spreads, looks almost like normal prostate gland tissue.  
 
Predicting future tumor behavior is obviously very important. How fast will it grow?  Is it likely to spread? How well can it be expected to respond to treatment?  As a result of decades of experience, doctors have learned to use the Gleason scoring system to accurately predict the long-term outcome in individual patients. The new GAT tests represent an important additional refinement, further enhancing our ability to predict the future behavior of an individual cancer. GAT holds one even bigger promise.  In the future we believe GAT testing will be a powerful aid in the selection of targeted therapy, i.e., picking cancer treatments with anticancer activity tailored to individual tumor types.  This hope, however, will have to be postponed until our limited armamentarium of effective treatments is further expanded.    
 
Now, what is it that I consider to be the most exciting area of medical progress? Since I am an impatient type of guy, someone who is looking for quick results, I find immunotherapy more exciting than GAT. To fully exploit the potential of GAT we will need to invent new pills for each of the myriad of genetically different tumor types. Immunotherapy on the other hand comes with its own “built-in” GAT system that enables it to target the unique genetic signature of individual cancer cells. The immune system is so smart, all we have to do is “flip the switch on” and starts cranking out genetically targeted anticancer therapy. Recent developments in the field of immunology are truly mind-boggling and hold promise for a big revolution in cancer therapy within the next 5-10 years.  I’ll try to address some of these recent advances in an upcoming blog.