Clinical Utility of Quantitative Gleason Grading in Prostate Biopsies and Prostatectomy Specimens

Sauter, Guido; Steurer, Stefan; Clauditz, Till S.; Krech, Till; Wittmer, Corinna; Lutz, Florian; Lennartz, Maximilian; Janssen, Tim Julian; Hakimi, Nayira; Simon, Ronald; Petersdorff-Campen, Mareike von; Jacobsen, Frank; Loga, Katharina von; Wilczak, Waldemar; Minner, Sarah; Tsourlakis, Maria Christina; Chirico, Viktoria; Haese, Alexander; Heinzer, Hans; Becher, Burkhard; Graefen, Markus; Michl, Uwe; Salomon, Georg; Steuber, Thomas; Budäus, Lars; Hekeler, Elena; Malsy-Mink, Julia; Kutzera, Sven; Fraune, Christoph; Göbel, Cosima; Huland, Hartwig; Schlomm, Thorsten

doi:10.1016/j.eururo.2015.10.029

Cited by 234 publications

(271 citation statements)

References 27 publications

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“…An abundance of data suggests that percentage of adenocarcinoma that is high-grade pattern 4/5 is an important prognostic indicator [29][30][31]. The method for determination of percentage of pattern 4 was not specified.…”

Section: Immunophenotypementioning

confidence: 99%

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours

et al. 2016

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It has been 12 yr since the publication of the last World Health Organization (WHO) classification of tumours of the prostate and bladder. During this time, significant new knowledge has been generated about the pathology and genetics of these tumours. Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 WHO classification. In most cases, it represents intraductal spread of aggressive prostatic carcinoma and should be separated from high-grade prostatic intraepithelial neoplasia. New acinar adenocarcinoma variants are microcystic adenocarcinoma and pleomorphic giant cell adenocarcinoma. Modifications to the Gleason grading system are incorporated into the 2016 WHO section on grading of prostate cancer, and it is recommended that the percentage of pattern 4 should be reported for Gleason score 7. The new WHO classification further recommends the recently developed prostate cancer grade grouping with five grade groups. For bladder cancer, the 2016 WHO classification continues to recommend the 1997 International Society of Urological Pathology grading classification. Newly described or better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential, which is frequently identified in patients with a prior history of urothelial carcinoma. Invasive urothelial carcinoma with divergent differentiation refers to tumours with some percentage of "usual type" urothelial carcinoma combined with other morphologies. Pathologists should mention the percentage of divergent histologies in the pathology report. PATIENT SUMMARY Intraductal carcinoma of the prostate is a newly recognized entity in the 2016 World Health Organization classification. Better defined noninvasive urothelial lesions include urothelial dysplasia and urothelial proliferation of uncertain malignant potential. v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j AbstractIt has been 12 yr since the publication of the last World Health Organization (WHO) classification of tumours of the prostate and bladder. During this time, significant new knowledge has been generated about the pathology and genetics of these tumours.

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Section: Immunophenotypementioning

confidence: 99%

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours

et al. 2016

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“…As quoted in a recent editorial by Egevad et al, "The reporting of percentage Gleason 4 tumor tissue has the advantage that this highlights if a cancer is at the lower or higher end of a grade" [12]. As shown by Sauter et al in a very recent publication, "there is a biological continuum within Gleason score 3 + 4 = 7 and 4 + 3 = 7 tumors that is reflected in clinical outcome" [13].…”

Section: Experts' Commentsmentioning

confidence: 99%

Prostate Cancer Glands with Cribriform Architecture and with Glomeruloid Features should be Considered as Gleason Pattern 4 and not Pattern 3

Minardi¹,

Mazzucchelli²,

Scarpelli³

et al. 2016

Future Oncol.

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“…In a recent analysis we have demonstrated that by using the percentage of unfavorable Gleason patterns, the Gleason grading can be transformed from a categorical into a continuous variable with an even finer distinction of prognostic subgroups [49]. That the prognostic impact of GGH expression largely disappeared in groups defined by Gleason grade categories or by comparable percentages of Gleason 4 patterns demonstrates the power of morphologic malignancy assessment.…”

Section: Discussionmentioning

confidence: 99%

“…Histopathological data were retrieved from the patients’ records, including tumor stage, Gleason grade, nodal stage and stage of the resection margin. In addition to the classical Gleason categories, “quantitative” Gleason grading was performed as described before [49]. In brief, for every prostatectomy specimen, the percentages of Gleason 3, 4, and 5 patterns were recorded in cancerous tissues as part of the regular process of Gleason grading.…”

Section: Methodsmentioning

confidence: 99%

High-Level γ-Glutamyl-Hydrolase (GGH) Expression is Linked to Poor Prognosis in ERG Negative Prostate Cancer

Melling

Rashed

Schroeder

et al. 2017

IJMS

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γ-glutamyl-hydrolase (GGH) is a ubiquitously-expressed enzyme that regulates intracellular folate metabolism for cell proliferation, DNA synthesis, and repair. Employing GGH immunohistochemistry on a tissue microarray with 12,427 prostate cancers, we found that GGH expression was negative to low in normal prostate epithelium, whereas 88.3% of our 10,562 interpretable cancers showed GGH expression. GGH staining was considered as low intensity in 49.6% and as high intensity in 38.6% of cancers. High GGH expression was linked to the TMPRSS2:ERG-fusion positive subset of cancers (p < 0.0001), advanced pathological tumor stage, and high Gleason grade (p < 0.0001 each). Further analysis revealed that these associations were merely driven by the subset of ERG-negative cancers, High GGH expression was weakly linked to early biochemical recurrence in ERG negative cancers (p < 0.0001) and independent from established histo-pathological parameters. Moreover, GGH expression was linked to features of genetic instability, including presence of recurrent deletions at 3p, 5q, 6q, and 10q (PTEN, p ≤ 0.01 each), as well as to accelerated cell proliferation as measured by Ki67 immunohistochemistry (p < 0.0001). In conclusion, the results of our study identify GGH as an ERG subtype specific molecular marker with modest prognostic relevance, which may have clinical relevance if analyzed in combination with other molecular markers.

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Clinical Utility of Quantitative Gleason Grading in Prostate Biopsies and Prostatectomy Specimens

Cited by 234 publications

References 27 publications

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours

Prostate Cancer Glands with Cribriform Architecture and with Glomeruloid Features should be Considered as Gleason Pattern 4 and not Pattern 3

High-Level γ-Glutamyl-Hydrolase (GGH) Expression is Linked to Poor Prognosis in ERG Negative Prostate Cancer

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