One indicator of severity used to evaluate men with newly diagnosed prostate cancer is the appearance of the cells obtained by biopsy. In 1966 Donald Gleason, a pathologist at Johns Hopkins University was able to identify five specific patterns of cancer cell architecture that could be seen under a low-powered microscope and proposed a classification of prostate cancer, based on how closely cancer cells resembled normal cells. The Gleason score for prostate cancer uses a grading system from 1 to 5, 1 being the most benign with cells that closely resembled normal cells, and 5 being the most malignant with cells that looked the least like normal prostate cells.
The Process of Gleason Grading
To determine a Gleason score, a pathologist studies the shape and architecture of tumor cells under a microscope, determining how clear-cut the cancer cells’ structure and edges are. The extent of which cancer cells resemble normal prostate cells is called differentiation, and is the key factor in determining a Gleason score. Prostate cancer cells which closely resemble normal prostate cells are considered well-differentiated. The architecture of normal, well-differentiated cells involves distinct, clearly defined borders. These prostate cancer cells have clear centers, like little round doughnuts, and tend to be the slowest growing and least dangerous of prostate cancers.
Poorly differentiated cancer cells, on the other hand, are typically very aggressive and fast growing, resulting in a high Gleason score. When prostate cancer cells become poorly differentiated, they appear to melt together into clumps. These cancers are the most malignant, running run rampant, sweeping through and damaging nearby tissue. These high Gleason score cancer cells no longer respect boundaries, either their own or those of normal cells. The results are often devastating. Without treatment, the fastest, most-out-of-control cancer cells can kill a man within several years of their initial presentation.
Gleason Grading and Prostate Cancer
The Gleason grading system assigns a number from 1 to 5, based on how closely the cells in the cancerous tissue resemble normal tissue:
|
Gleason Score |
Resemblance to Normal Prostate Cells |
|
1 |
Cancer cells with this Gleason score are well differentiated, and look most like normal prostate cells. Arranged in a compact mass, they have a relatively normal architecture and clearly defined borders. Grade 1 prostate cancer cells are considered low grade and tend to be less aggressive than higher grade cancers. |
|
2 |
Cancer cells with this Gleason score are still well differentiated, however, their arrangement appears more irregular, with cell clusters that occasionally seen to invade surrounding tissues. |
|
3 |
Cancer cells with this Gleason score are more moderately differentiated. Their arrangement is very irregular, with many cell clusters often invading surrounding prostate tissue. Grade 3 cancer cells are the most commonly discovered in biopsy specimens. |
|
4 |
Cancer cells with this Gleason score are poorly differentiated and have distorted shapes. There is evidence that there is a progressive invasion of surrounding prostate tissues by cancerous cell clusters. |
|
5 |
Cancer cells with this Gleason score are undifferentiated and bear no resemblance to normal prostate cells. They are completely distorted and seem to melt together. They are no longer arranged in any formal clusters and are referred to as high grade cancer. |
From the point of view of prognosis, Gleason grading for prostate cancer is not a continuum. The gaps between Gleason score grades 1 and 2 and grades 2 and 3 are not large, and men with all three cancer cell types typically have a favorable diagnosis. On the other hand, the gap between Gleason score grades 3 and 4 is significant. Men with Gleason score 4 cells have a 30% higher risk metastatic cancer, in which the disease spreads, and spreads more quickly. Men with prostate cancer and a Gleason score 5 have a much worse prognosis. Fortunately today, with earlier screening a diagnosis, these men are few in number. One study suggested that the percentage of grade 4 and 5 in a tumor was the single best predictor of prostate cancer recurrence.
Doing the Math of a Gleason Score for Prostate Cancer
The Gleason grading of prostate cancer cells can seem confusing and complicated, but it comes down to adding two numbers. Unlike most cancers, prostate cancer is multi-focal, meaning that men with prostate cancer typically have foci cancer cells in different areas in their prostate glands. Aware of its multi-focal nature, Gleason suggested that a prostate cancer tumor be classified twice. He found that adding the number of the most common pattern to the number of the second most common pattern resulted in a score, which proved more accurate at classifying prostate cancer than just picking one pattern alone:
- The first number grade, or Gleason score, is determined by the cancerous cell type that is most frequently found.
- The second number grade, or Gleason score, is then determined by the second, most frequent cancerous cell type.
- Both of these numbers are added for a total Gleason score for prostate cancer, which ranges from the lowest of 2 (1+1) to the highest of 10 (5+5).
Fewer than 2% of men who have a needle biopsy have a Gleason score of 2, 3, or 4 prostate cancer. Men with these low grade prostate cancer cells are rarely diagnosed by biopsy, because these cancers do not normally call attention to themselves by increasing a man’s prostate-specific antigen (PSA) level. They are the least aggressive and the least likely to metastasize. These slow-growing prostate cancers show up in as many as half of all men by age eighty. When such tumors are discovered, they are most often found in the transition zone, typically in tissue samples from a routine transurethral resection of the prostate (TUR). Generally considered harmless, they usually are managed with watchful waiting.
The vast majority of men diagnosed with prostate cancer fall right in the middle of the Gleason grading system, with Gleason scores of 5, 6 and 7. A Gleason score of 5 or less is very good. A Gleason score of 6 (3+3) is still very good and the most commonly reported in prostate biopsies, because it means under the microscope, the pathologist only identified grade 3 cells. Gleason scores 5 and 6 are much alike; they behave similarly and are both relatively slow-growing cancer-the kind of cancers that can be cured.
A Gleason 7 score is also common and is somewhat problematic for the Gleason grading system. When talking to your doctor about a Gleason 7 score, it is important to know which tumor grade is predominant. To get a Gleason 7 score, one part of the equation must be a grade 3, and the other a grade 4. There is a notable difference between a Gleason 3+4 grading, in which most of the cancer is a Gleason 3 score, and a Gleason 4+3 score, in which most of the cancer is a Gleason 4 score. It is now known that tumors with more Gleason 4 score behave aggressively.
The seriousness of a Gleason score of 7 (3+4) or 7(4+3) depends on the percentage of grade 4 cells present. If the Gleason 7 score is a 3+4, it means that grade 4 constitutes less than 50%; they could be as low as 5% and as high as 45% (Gleason gradings are done in increments of 5%). If, on the other hand, the Gleason grading of 7 resulted from 4+3, then grade 4 cells are the majority and could be as high as 95%. Grade 4 cells are significantly more malignant than grade 3 cells, so it is important to know whether a Gleason score of 7 is a 3+4 or a 4+3.
A Gleason score of 7, or 3+4 Gleason grading means the tumor has fewer grade 4 cells and could have a relatively favorable prognosis, closer to that of man with a Gleason 6 prostate cancer, and a Gleason 7 grading of a 4+3, means a high percentage of grade 4 cells and a less favorable prognosis, one closer to a man who has a Gleason 8 score and prostate cancer. One study, of over 2,000 prostate cancers, indicated that men with a Gleason grading of 7 that consisted of a 4+3, had had a recurrence rate at 7 and 10 years double than those with a Gleason score 7 (3+4). So while both a 3+4 and a 4+3 result in a Gleason 7 score, the 4+3 is more aggressive.
However, a Gleason 7 score is still much different and more favorable than a Gleason 8 score. A Gleason grading of 8 or more is not at all favorable. Fortunately, only high-grade tumors, those with Gleason scores of 8, 9
Prostate cancers with a high Gleason scores are considered margin-positive, which is cancer that has penetrated the prostate wall and cannot be fully removed by surgery. A high Gleason grading means it is likely the cancer cells have spread to the seminal vesicles. At this point of its growth, the prostate cancer is more resistant to treatment, in comparison to prostate cancer with a lower Gleason score. For prostate cancer patients with a high Gleason grading, they face a higher likelihood of cancer spreading to their lymph nodes. If you have a high Gleason score, there is a greater probability that the cancer has spread beyond your prostate wall. Ultimately, your prognosis depends on several additional factors, including how far the tumor has spread within your body, your age and health history, all of which your doctor should explain to you along with options for treatment.
