Physicians use the term "grade" to describe the appearance of thin slices of cancer tissue when it is observed under a microscope. In the case of prostate cancer tissue, the most common system used in the USA to grade the appearance of this tissue is called the Gleason grading system, after the physician who first described this system.
The Gleason grading system is not the only grading system in use around the world. However, because it is the one most commonly used in the USA, it is the one we will try to explain here. If your physician talks to you about the grade of your prostate cancer, you may want to ask if it is the Gleason grade that he or she is referring to.
The Gleason grade is one of several pieces of information determined by the pathologist who examines the biopsy specimen taken from the prostate. Readers wishing to understand more about the role of the pathologist in the diagnosis of prostate cancer may wish to read the article entitled "The pathologic examination of prostate tissue", which addresses this topic in detail, and which also explains the importance to the patient of receiving a copy of his pathology report.
The Gleason system is based exclusively on the architectural pattern of the glands of the prostate tumor. It evaluates how effectively the cells of any particular cancer are able to structure themselves into glands resembling those of the normal prostate. The ability of a tumor to mimic normal gland architecture is called its differentiation, and experience has shown that a tumor whose structure is nearly normal (well differentiated) will probably have a biological behavior relatively close to normal -- that is not very aggressively malignant.
The principle is fairly simple, and Gleason grading from very well differentiated (grade 1) to very poorly differentiated (grade 5) is usually done for the most part by viewing the low magnification microscopic image of the cancer. There are important additional details which require higher magnification, and an ability to accurately grade any tumor is achieved only through much training and experience in pathology.
Dr. Gleason has provided a conceptual diagram (oversimplified) in Figure 1 to show the continuum of deteriorating cancer cell architecture, and the four dividing lines along this continuum which he discovered are able to identify patients with significantly different prognosis derived from a study which included 2,900 patients.
Figure 1: This illustration shows Dr Gleason's own simplified drawing of the five Gleason grades of prostate cancer. Grade 1 appears on the far left and grade 5 on the far right. Adapted from Gleason DF. The Veteran's Administration Cooperative Urologic Research Group: histologic grading and clinical staging of prostatic carcinoma. In Tannenbaum M (ed.) Urologic Pathology: The Prostate. Lea and Febiger, Philadelphia, 1977; 171-198.
In the illustrations and text that follow, we have given real examples of tissues which show the five Gleason grades and tried to describe the differences between them. We would like to thank Dr John McNeal of the Department of Urology, Stanford University School of Medicine, for kindly providing these illustrations and assisting us in developing this information.
Figure 2: Grade 1 (left) and grade 2 (right) protate adenocarcinoma. Both have pale cells and well formed, separate glands with lumens. Grade 1 is more compact (less invasive) than grade 2. Illustration courtesy of John E. McNeal, MD, Department of Urology, Stanford University School of Medicine.
Figure 7 shows only a sea of black nuclei with no pattern. The variety of different appearances is less than for grade 4 because there are fewer ways to do nothing! This grade is often called undifferentiated, because its features are not significantly distinguishing to make it look any different from undifferentiated cancers which occur in other organs. Figure 7: Grade 5 adenocarcinoma, consisting of sheets of cells whose lack of pattern in nuclear arrangement indicates total loss of architecture, seen at higher magnification. Illustration courtesy of John E. McNeal, MD, Department of Urology, Stanford University School of Medicine.
If you are interested in seeing other examples of samples showing Gleason grades, try looking at the materials from the University of Pittsburgh Medical Center. In particular, they show several examples of grades 3 and 4.
When a pathologist looks at prostate cancer specimens under the microscope and gives them a Gleason grade, he or she in fact will always try to identify two architectural patterns and assign a Gleason grade to each one. There may be a primary or most common pattern and then a secondary or second most common pattern which the pathologist will seek to describe for each specimen; alternatively, there may often be only a single pure grade.
In developing his system, Dr Gleason discovered that by giving a combination of the grades of the two most common patterns he could see in any particular patient's specimens, he was better able to predict the likelihood that that particular patient would do well or badly. Therefore, even though it may seem confusing, the Gleason score which a physician usually gives to a patient is actually a combination or sum of two numbers. These combined Gleason sums or scores may be determined as follows:
The grade of a prostate cancer specimen is very valuable to doctors in helping them to understand how a particular case of prostate cancer can be treated. In general, the time for which a patient is likely to survive following a diagnosis of prostate cancer is related to the Gleason score. The lower the Gleason score, the better the patient is likely to do.
However, remember that prostate cancer is a very complicated disease. People with low Gleason scores have been known to fare poorly and men with high Gleason scores have been known to do well. General principles do not always apply to individual patients.
By combining the patient's Gleason score with his PSA level and the clinical stage estimated by the physician, it is possible to use the Partin coefficient tables to estimate the likelihood that that patient has localized or locally advanced prostate cancer of different types.