The Gleason grading system is used to help evaluate the prognosis of patients with prostate cancer using samples from a prostate biopsy. Together with other parameters, it is incorporated into a strategy of prostate cancer staging which predicts prognosis and helps guide therapy. A Gleason score is given to prostate cancer based upon its microscopic appearance. Cancers with a higher Gleason score are more aggressive and have a worse prognosis. Pathological scores range from 2 to 10, with higher numbers indicating greater risks and higher mortality. The system is widely accepted and used for clinical decision making even as it is recognised that certain biomarkers, like ACP1 expression, might yield higher predictive value for future disease course. The histopathologic diagnosis of prostate cancer has implications for the possibility and methodology of Gleason scoring. For example, it is not recommended in signet-ring adenocarcinoma or urothelial carcinoma of the prostate, and the scoring should discount the foamy cytoplasms seen in foamy gland carcinoma. A total score is calculated based on how cells look under a microscope, with the first half of the score based on the dominant, or most common cell morphology (scored 1 to 5), and the second half based on the non-dominant cell pattern with the highest grade (scored 1 to 5). These two numbers are then combined to produce a total score for the cancer.
Specimens and processing Most often, a urologist or radiologist will remove a cylindrical sample (biopsy) of prostate tissue through the rectum (or, sometimes the perineum), using hollow needles, and biomedical scientists in a histology laboratory prepare microscope slides for H&E staining and immunohistochemistry for diagnosis by a pathologist. If the prostate is surgically removed, a pathologist will slice the prostate for a final examination.
Histologic patterns
A pathologist microscopically examines the biopsy specimen for certain "Gleason" patterns. These Gleason patterns are associated with the following features:
Pattern 1 – The cancerous prostate closely resembles normal prostate tissue. The glands are small, well-formed, and closely packed. This corresponds to a well differentiated carcinoma. Pattern 2 – The tissue still has well-formed glands, but they are larger and have more tissue between them, implying that the stroma has increased. This also corresponds to a moderately differentiated carcinoma. Pattern 3 – The tissue still has recognizable glands, but the cells are darker. At high magnification, some of these cells have left the glands and are beginning to invade the surrounding tissue or having an infiltrative pattern. This corresponds to a moderately differentiated carcinoma. Pattern 4 – The tissue has few recognizable glands. Many cells are invading the surrounding tissue in neoplastic clumps. This corresponds to a poorly differentiated carcinoma. Pattern 5 – The tissue does not have any or only a few recognizable glands. There are often just sheets of cells throughout the surrounding tissue. This corresponds to an anaplastic carcinoma. In the present form of the Gleason system, prostate cancer of Gleason patterns 1 and 2 are rarely seen. Gleason pattern 3 is by far the most common.
Primary, secondary and tertiary grades After analyzing the tissue samples, the pathologist then assigns a grade to the observed patterns of the tumor specimen.
Primary grade – assigned to the dominant pattern of the tumor (has to be greater than 50% of the total pattern seen). Secondary grade – assigned to the next-most frequent pattern (has to be less than 50%, but at least 5%, of the pattern of the total cancer observed). Tertiary grade – increasingly, pathologists provide details of the "tertiary" component. This is where there is a small component of a third (generally more aggressive) pattern.
Scores and prognoses The pathologist then sums the pattern-number of the primary and secondary grades to obtain the final Gleason score. If only two patterns are seen, the first number of the score is that of the tumor's primary grade while the second number is that of the secondary grade, as described in the previous section. If three patterns are seen, the first number of the score would be the primary grade and the second number the pattern with the highest grade. For example, if the primary tumor grade was 2 and the secondary tumor grade was 3 but some cells were found to be grade 4, the Gleason score would be 2+4=6. This is a slight change from the pre-2005 Gleason system where the second number was the secondary grade (i.e., the grade of the second-most common cell line pattern).
Key- blue: Gleason pattern 3 region, yellow: Gleason pattern 4 region, red: Gleason pattern 5 region
Gleason scores range from 2 to 10, with 2 representing the most well-differentiated tumors and 10 the least-differentiated tumors. Gleason scores have often been categorized into groups that show similar biologic behavior: low-grade (well-differentiated), intermediate-grade, moderate to poorly differentiated or high-grade. More recently, an investigation of the Johns Hopkins Radical Prostatectomy Database (1982–2011) led to the proposed reporting of Gleason grades and prognostic grade groups as:
Gleason score ≤ 6 (prognostic grade group I); Gleason score 3+4=7 (prognostic grade group II) indicating the majority is pattern 3; Gleason score 4+3=7 (prognostic grade group III) where pattern 4 is dominant; Gleason score 4+4=8 (prognostic grade group IV); Gleason scores 9–10 (prognostic grade group V). Prostate cancers with a Gleason score ≤ 6 usually have rather good prognoses.
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