Prostate cancer grading in 2018: limitations, implementations, cribriform morphology, and biological markers

The Gleason grading system is among the most important prognostic factors in patients with prostate cancer. From the 2005 to the 2014 consensus conferences, organized by the International Society of Urological Pathology, the morphologic criteria for the identification of the Gleason patterns were redefined, thus resulting in the shrinkage of the Gleason pattern 3. This led to the expansion of the Gleason pattern 4. The newly proposed grade group system reduces the Gleason scores of prostate cancer to the lowest number, each associated with a unique behavior from the prognostic point of view. The advantage is that the simplified system with five groups allows for a more accurate stratification of the patients in comparison with the Gleason system. Cribriform, fused, ill-defined and glomeruloid glands are part of the histologic spectrum of the Gleason pattern 4. Cribriform morphology has a prognosis that is worse in comparison with the other non-cribriform Gleason 4 patterns. One of the major implications of the cribriform growth is that it precludes a patient from choosing active surveillance.

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Intraductal Carcinoma of Prostate (IDC-P), Grade Group, and Molecular Pathology: Recent Advances and Practical Implication

annals of urologic oncology ◽

10.32948/auo.2019.03.11 ◽

2019 ◽

pp. 1-10

Author(s):

Ashwyna Sunassee ◽

Ghadah Al Sannaa ◽

Jae Y. Ro

Keyword(s):

Prostate Cancer ◽

Molecular Pathology ◽

Invasive Carcinoma ◽

World Health ◽

Intraductal Carcinoma ◽

Grading System ◽

Grade Group ◽

Group System ◽

Gleason Grading ◽

Recent Advances

The Gleason grading system for prostatic carcinoma is widely used internationally and is based on microscopic architectural patterns of tumors. Over the years, there have been modifications to the original grading system established by Donald F Gleason in 1966 and refined in 1974 which have subsequently been established by the World Health Organization in its WHO Classification of Tumors of the Urinary System and Male Genital Organs book, published in 2016. There have been certain practical issues associated with the changes, of note, the addition of intraductal carcinoma of prostate (IDC-P), which unlike its breast counterpart rarely occurs in isolation without association with invasive carcinoma and tends to be associated with high-grade invasive carcinoma. In addition, the Grade group system has been introduced which categorizes tumors into prognostically relevant groups based on the histological grade scores. The grade group system brings to light the importance of making accurate scoring and subsequent grouping of the tumors as it affects the clinical treatment, prognostic implication and stage assignment. Molecular pathology of the prostate is not widely utilized in clinical practice, but is emerging. The most common genomic aberration in prostate cancer includes gene fusion, amplification, deletion, and mutation. In addition, up and down regulation of gene expression in critical cellular pathways is also at play. A series of long noncoding RNA expression changes have been also unveiled from transcriptome sequencing data. They play a regulatory role in prostate cancer and are promising diagnostic and potentially prognostic markers as well as molecular treatment strategy. In this review, we summarize recent advances in molecular pathology of prostate cancer and their emerging clinical utility with currently available molecular tests. In this review article, we discuss the followings: 1) Gleason grading system with its modification, 2) Grade group, 3) Intraductal carcinoma, and 4) molecular pathology. Additionally, we present that molecular studies continue to emerge, and there is significant opportunity for targeted therapeutic options that remains to be explored in depth.

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Evaluation of Gleason Grade Group 5 in a Contemporary Prostate Cancer Grading System and Literature Review

Clinical Genitourinary Cancer ◽

10.1016/j.clgc.2020.08.001 ◽

2020 ◽

Author(s):

Rei Kamitani ◽

Kazuhiro Matsumoto ◽

Takeo Kosaka ◽

Toshikazu Takeda ◽

Akinori Hashiguchi ◽

...

Keyword(s):

Prostate Cancer ◽

Literature Review ◽

Grading System ◽

Gleason Grade ◽

Grade Group ◽

Group 5 ◽

Cancer Grading

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Understanding the gleason grading system and its changes

Journal of Pathology of Nepal ◽

10.3126/jpn.v9i2.25723 ◽

2019 ◽

Vol 9 (2) ◽

pp. 1580-1585

Author(s):

Sujata Pudasaini ◽

Neeraj Subedi

Keyword(s):

Prostatic Carcinoma ◽

World Health ◽

Grading System ◽

Pathology Report ◽

Gleason Grade ◽

High Grade ◽

Grade Group ◽

Gleason Grading ◽

Gleason Pattern ◽

Health Organization

Gleason Grading System is the most widely used grading system used for prostatic carcinoma. The five basic grade patterns are used to generate a histologic score, which can range from 2 to 10 (including primary and secondary patterns). The original Gleason Grading System was used to grade acinar adenocarcinoma based on architectural features and it has been correlated with excellent clinical outcomes. Since 1960s, after the discovery of the original Gleason Grading System, a modified version of the Gleason Grading System was introduced in the International Society of Urological Pathology 2005 which came up with many changes including elimination of Gleason pattern 1. The ISUP 2005 was further updated in 2014 to provide more accurate stratification of prostatic carcinoma. The new Gleason Grade Group 1 to 5 has been introduced and it has little resemblance to the original Gleason system. This Gleason Grade Group has been accepted by the 2016 World Health Organization classification of tumors of the prostate. For a needle biopsy, high grade component of any quantity should be included in the Gleason score as it indicates a high probability of finding significant high grade tumor in the prostate. By understanding the principles and practice of this grading system, the pathology report has to clearly indicate which system is adopted in the reporting. This review discusses GGS and its recent development focusing on major changes over the years that led to the new Grade Group system proposed by the 2014 ISUP consensus.

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Prostate Cancer Grading: A Decade After the 2005 Modified Gleason Grading System

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2015-0487-sa ◽

2016 ◽

Vol 140 (10) ◽

pp. 1140-1152 ◽

Cited By ~ 41

Author(s):

Oleksandr N. Kryvenko ◽

Jonathan I. Epstein

Keyword(s):

Prostate Cancer ◽

Radical Prostatectomy ◽

International Society ◽

Current Concept ◽

Johns Hopkins Hospital ◽

Grading System ◽

Gleason Grading ◽

Multiple Cores ◽

Modified Gleason Grading ◽

Cancer Grading

Since 1966, when Donald Gleason, MD, first proposed grading prostate cancer based on its histologic architecture, there have been numerous changes in clinical and pathologic practices relating to prostate cancer. Patterns 1 and 2, comprising more than 30% of cases in the original publications by Gleason, are no longer reported on biopsy and are rarely diagnosed on radical prostatectomy. Many of these cases may even have been mimickers of prostate cancer that were described later with the use of contemporary immunohistochemistry. The original Gleason system predated many newly described variants of prostate cancer and our current concept of intraductal carcinoma. Gleason also did not describe how to report prostate cancer on biopsy with multiple cores of cancer or on radical prostatectomy with separate tumor nodules. To address these issues, the International Society of Urological Pathology first made revisions to the grading system in 2005, and subsequently in 2014. Additionally, a new grading system composed of Grade Groups 1 to 5 that was first developed in 2013 at the Johns Hopkins Hospital and subsequently validated in a large multi-institutional and multimodal study was presented at the 2014 International Society of Urological Pathology meeting and accepted both by participating pathologists as well as urologists, oncologists, and radiation therapists. In the present study, we describe updates to the grading of prostate cancer along with the new grading system.

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SOCS3 immunohistochemical expression to support the 2005 International Society of Urological Pathology (ISUP) modified Gleason grading system.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.216 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 216-216

Author(s):

Gian Luigi Petrone ◽

Francesco Pierconti ◽

Maurizio Martini ◽

Tonia Cenci ◽

Luigi Maria Larocca

Keyword(s):

Gleason Score ◽

International Society ◽

Consensus Conference ◽

Point Of View ◽

Cytokine Signaling ◽

Grading System ◽

Exact Tests ◽

Gleason Grading ◽

Gleason Pattern ◽

Modified Gleason Grading

216 Background: In the 2005 International Society of Urological Pathology (ISUP) Consensus Conference, a modified Gleason grading system for prostate cancer was proposed. (Epstein JI et al. Am J Surg Pathol 2005; 29:1228-1242) Afterwards an interobserver study among experts in genitourinary pathology proposed some modifications and refinements to the 2005 ISUP modified grading system concerning the cribriform pattern carcinoma that it should never be diagnosed as Gleason pattern 3, assigning Gleason pattern 4 to cribriform glands (Latour M et al. Am J Surg Pathol 2008; 32: 1532-1539; Epstein J I Journal of Urology 2010: 183:433-440). Methods: The study population consisted of 80 patients undergoing biopsies at the Institute of Urology of our hospital, between February 2012 and January 2013 stratified into 3 different categories on the basis of histologic pattern: 1) 20 patients with classical and modified Gleason score 3+3 = 6; 2) 30 patients with classical Gleason score 3+3 = 6 upgraded to Gleason score 7 according to the ISUP modified grading system; and 3) 30 patients with classical and modified Gleason score 3+4 = 7. We evaluate the immunohistochemical protein expression of the suppressor of cytokine signaling (SOCS) proteins 3 (SOCS3) in these three different group of prostatic cancer biopsies. Results: We found that the SOCS3 pattern staining negative (-) or with SOCS3 negative staining with weak intensity staining in less than 50% of neoplastic glands (+/-) increases progressively in concomitance with the rise of Gleason score and SOCS3 positivity (+), correlates with classical or modified Gleason score 6 (P = 0,0004 Fisher’s exact tests) and with classical Gleason score 3+3 = 6 upgraded to Gleason score 7 (P = 0,0010 Fisher’s exact tests). Conclusions: In conclusion our data seem to support from a molecular point of view the modified criteria by 2005 International Society of Urological Pathology (ISUP) Consensus Conference as well as the hypothesis that the diagnosis of Gleason cribriform pattern 3 virtually does not exist and cribriform glands-regardless of their size-are nearly always considered pattern 4.

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The validation of the 2014 International Society of Urological Pathology (ISUP) grading system for patients with high-risk prostate cancer: A single-center retrospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.128 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 128-128

Author(s):

Jiandong Liu

Keyword(s):

Prostate Cancer ◽

High Risk ◽

International Society ◽

Biochemical Recurrence ◽

Predictive Accuracy ◽

Predictive Ability ◽

Grading System ◽

Grade Group ◽

High Risk Prostate Cancer ◽

Gleason Pattern

128 Background: Since the new 2014 grading system was recommended by the International Society of Urological Pathology (ISUP), it has been validated in patients with localized prostate cancer (PCa) and has shown excellent prognostic value. However, its predictive power in high-risk PCa remained unclear. Methods: Overall, 420 patients with high-risk PCa who underwent radical prostatectomy (RP) were included. Biochemical recurrence-free survival (BRFS) was set as the endpoint. Results: Biochemical recurrence occurred in 84/420 (20.0%) patients at the end of follow-up. Compared to the three-tier grouping system, the five-tier grouping system could more effectively distinguish the BRFS of patients with higher predictive accuracy (C-index: 0.599 vs 0.646). The BRFS of patients with grade group (GG) 1 and GG 2 was similar (p = 0.593). Also, the prognosis between those in the GG 2 and GG 3 could be clearly distinguished (p = 0.001). Whereas the discrimination capacity between patients with GG 3 and GG 4 was limited (p = 0.681). The high proportion of tertiary Gleason pattern 5 (TGP5) among patients with GG 3 might be an important confounder leading to the overlap of survival between GG 4 and GG 3. Conclusions: This study is the first one to validate the new 2014 ISUP grading system in patients with high-risk PCa who underwent RP. The 2014 system could effectively separate patients into five groups with high predictive accuracy. Notably, the existence of TGP5 needs to be routinely reported in clinical practice, which could help to support the predictive ability of the new grading system.

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Prostate Cancer Grading: A Decade After the 2005 Modified Gleason Grading System

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2016-0300-le ◽

2017 ◽

Vol 141 (2) ◽

pp. 182-183 ◽

Cited By ~ 2

Author(s):

Brett Delahunt ◽

David J. Grignon ◽

Hemamali Samaratunga ◽

John R. Srigley ◽

Katia R. M. Leite ◽

...

Keyword(s):

Prostate Cancer ◽

Grading System ◽

Gleason Grading ◽

Modified Gleason Grading ◽

Cancer Grading

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Prognostic significance of contemporary prostate cancer grading system in tumours with positive surgical margins

10.26226/morressier.578f37ffd462b8028d890475 ◽

2016 ◽

Author(s):

Gordana Dordevic

Keyword(s):

Prostate Cancer ◽

Prognostic Significance ◽

Surgical Margins ◽

Grading System ◽

Positive Surgical Margins ◽

Cancer Grading

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Interchangeability of light and virtual microscopy for histopathological evaluation of prostate cancer

Scientific Reports ◽

10.1038/s41598-021-82911-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Renata Zelic ◽

Francesca Giunchi ◽

Luca Lianas ◽

Cecilia Mascia ◽

Gianluigi Zanetti ◽

...

Keyword(s):

Prostate Cancer ◽

Virtual Microscopy ◽

Observer Agreement ◽

Gleason Grade ◽

Gleason Grading ◽

Gleason Pattern ◽

Inter Observer Variability ◽

Histopathological Evaluation ◽

Good Repeatability ◽

Repeatability And Reproducibility

AbstractVirtual microscopy (VM) holds promise to reduce subjectivity as well as intra- and inter-observer variability for the histopathological evaluation of prostate cancer. We evaluated (i) the repeatability (intra-observer agreement) and reproducibility (inter-observer agreement) of the 2014 Gleason grading system and other selected features using standard light microscopy (LM) and an internally developed VM system, and (ii) the interchangeability of LM and VM. Two uro-pathologists reviewed 413 cores from 60 Swedish men diagnosed with non-metastatic prostate cancer 1998–2014. Reviewer 1 performed two reviews using both LM and VM. Reviewer 2 performed one review using both methods. The intra- and inter-observer agreement within and between LM and VM were assessed using Cohen’s kappa and Bland and Altman’s limits of agreement. We found good repeatability and reproducibility for both LM and VM, as well as interchangeability between LM and VM, for primary and secondary Gleason pattern, Gleason Grade Groups, poorly formed glands, cribriform pattern and comedonecrosis but not for the percentage of Gleason pattern 4. Our findings confirm the non-inferiority of VM compared to LM. The repeatability and reproducibility of percentage of Gleason pattern 4 was poor regardless of method used warranting further investigation and improvement before it is used in clinical practice.

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