Clinical implications of changing definitions within the Gleason grading system

Abstract

Remarkably, more than 40 years after the inception of the Gleason grading system, it remains one of the most powerful prognostic predictors in prostate cancer. Gleason's original grading system, however, has undergone significant revision over the years, first by Gleason and his colleagues, and most recently at the 2005 International Society of Urological Pathology Consensus Conference. The consensus conference and subsequent articles proposing further modifications have helped pathologists to adapt the Gleason grading system to current urologic practice in a uniform manner. The changing definitions of Gleason pattern 3 and 4 prostatic adenocarcinoma have tended to narrow the scope of pattern 3 carcinoma and widen the scope of pattern 4 carcinoma. These modifications have had an important role in improving the inter-observer reproducibility of the Gleason system. Whether these changes have a significant impact on the clinical treatment of prostate cancer remains to be seen. However, as many of these modifications are supported only by a few studies, long-term follow-up studies with clinical end points are essential to validate these recommendations.

Implications of the International Society of Urological Pathology Modified Gleason Grading System

“…Today's cases of Gleason score 6 are a homogenous group of tumors lacking cribriform and poorly formed glands, and are, therefore, associated with a better prognosis. An example can be seen in a study 20 analyzing 38 cases that were diagnosed before the consensus conference as organconfined, margin negative, Gleason score 6 PCa, which were treated with radical prostatectomy in 1983-2005 and which had biochemical progression. On review of these older Gleason score 6 cases, 24 (63%) would be considered to have some Gleason pattern 4 under today's grading scheme, including poorly formed, fused, or cribriform glands.…”

“…19,20,36 This recommendation has been based on a reproducibility study by Latour et al 37 and is supported by nuclear DNA studies. Latour et al 37 selected 30 needle biopsy cases that possibly represented cribriform Gleason pattern 3 cancer.…”

“…Because sampling is an unavoidable issue on needle biopsy, it is unlikely that any refinement of the Gleason system will make the distinction between 3 + 4 5 7 and 4 + 3 5 7 into a reliable basis for determining appropriate therapy at this time. 20 There is also a need to better define the detection threshold for a small amount of Gleason pattern 5. Experts have claimed that they require a cohesive focus of epithelial structures without lumina, seen at a power lower than 340.…”

“…The general theme of the changes to patterns 3 and 4 was to limit the definition of pattern 3 carcinoma and to widen the scope of pattern 4 carcinoma 19,20 (Table 7). As in the original Gleason description, pattern 3 carcinomas are composed of discrete, circumscribed, and infiltrative glands with well-formed glandular lumina.…”

ETS fusion genes in prostate cancer

“…Almost all prostate cancers are adenocarcinomas and it is generally accepted that prostate cancers develop from a precursor stage denoted as prostate intraepithelial neoplasia (PIN; DeMarzo et al 2003). Growth patterns of tumors can be very different and heterogeneous, reflected in the so-called Gleason grade (Lotan & Epstein 2010). Similar to other tumors, prostate cancer growth is driven by the accumulation of genetic and epigenetic alterations.…”