Gleason score in prostate cancer

Last reviewed 09/2022

• Gleason grading system is a powerful tool to prognosticate and aid in the treatment of men with prostate cancer
  • needle biopsy Gleason score correlates with virtually all other pathological variables (including tumour volume and margin status in radical prostatectomy specimens, serum prostate-specific antigen levels and many molecular markers)
  • Gleason score assigned to the tumour at radical prostatectomy is the most powerful predictor of progression after radical prostatectomy (1)
  • there are however concerns about inter-observer variation in interpretation of Gleason scoring (2,3)
  • Gleason grading system is based on glandular architecture - nuclear atypia is not evaluated
    • Gleason grading system defines five histological patterns or grades with decreasing differentiation. The primary and secondary pattern, i.e. the most prevalent and the second most prevalent pattern, are added to obtain a Gleason score or sum
      • Gleason pattern 1
        • composed of a very well circumscribed nodule of separate, closely packed glands which do not infiltrate into adjacent benign prostatic tissue
        • glands are of intermediate size, and similar in size and shape
        • pattern is usually seen in transition zone cancers
        • Gleason pattern 1 is exceedingly rare
      • Gleason pattern 2
        • composed of round or oval glands with smooth ends. The glands are more loosely arranged and not quite as uniform in size and shape as those of Gleason pattern 1
        • may be minimal invasion by neoplastic glands into the surrounding non-neoplastic prostatic tissue
        • glands are of intermediate size and larger than in Gleason pattern 1
        • variation in glandular size and separation between glands is less than that seen in pattern 3.
        • Gleason pattern 2 is usually seen in transition zone cancers but may occasionally be found in the peripheral zone
      • Gleason pattern 3
        • the most common histological pattern
        • the glands are more infiltrative and the distance between them is more variable than in patterns 1 and 2
          • malignant glands often infiltrate between adjacent non-neoplastic glands
          • glands of pattern 3 vary in size and shape and are often angular
            • small glands are typical for pattern 3, but there may also be large, irregular glands
              • each gland has an open lumen and is circumscribed by stroma
      • Gleason pattern 4
        • glands appear fused, cribriform or they may be poorly defined. Fused glands are composed of a group of glands that are no longer completely separated by stroma
        • edge of a group of fused glands is scalloped and there are occasional thin strands of connective tissue within this group
        • hypernephroid pattern described by Gleason is a rare variant of fused glands, with clear or very pale-staining cytoplasm
      • Gleason pattern 5
        • an almost complete loss of glandular lumina, with only occasional lumina apparent
        • epithelium forms solid sheets, solid strands or single cells invading the stroma
• needle biopsy Gleason score also correlates with virtually all other pathological variables, including tumour volume and serum PSA levels and many molecular markers
  • Gleason score is based on the sum of two numbers:
    • the first number is the score of the most common tumour pattern, the second number is the score of the second most common pattern if there are three patterns the first number is the most common and the second is the one with the highest grade
      • for example, if the most common tumor pattern was grade 3, but some cells were found to be grade 4, the Gleason Score would be 3+4 = 7
      • Gleason Score ranges from 0 to 10, with 10 having the worst prognosis
        • for Gleason Score 7, a Gleason 4+3 is a more aggressive cancer than a Gleason 3+4. Also, there is not really any difference between the aggressiveness of a Gleason Score 9 or 10 tumour
        • low grade tumours are with a score of 5 or below ; intermediate grade with a score of 6 & high grade of 7 or more till 10
• Gleason scores of 7-10 are associated with worse prognoses, and tumours with Gleason scores 5-6 are associated with lower progression rates after definitive therapy

Reference:

• (1) Montironi R et al. Gleason grading of prostate cancer in needle biopsies or radical prostatectomy specimens: contemporary approach, current clinical significance and sources of pathology discrepancies.BJU Int. 2005 Jun;95(8):1146-52.
• (2) Griffiths DF et al. A study of Gleason score interpretation in different groups of UK pathologists; techniques for improving reproducibility.Histopathology. 2006 May;48(6):655-62.
• (3) Melia J et al. A UK-based investigation of inter- and intra-observer reproducibility of Gleason grading of prostatic biopsies.Histopathology. 2006 May;48(6):644-54