Prostate cancer growth patterns beyond the Gleason score: entering a new era of comprehensive tumour grading

The Gleason grading system is one of the most important factors in clinical decision‐making for prostate cancer patients, and is entirely based on the classification of tumour growth patterns. In recent years it has become clear that some individual growth patterns themselves have independent prognostic value, and could be used for better personalised risk stratification. In this review we summarise recent literature on the clinicopathological value and molecular characteristics of individual prostate cancer growth patterns, and show how these, most particularly cribriform architecture, could alter treatment decisions for prostate cancer patients.

[1]  J. Epstein,et al.  Can Basal Cells Be Seen in Adenocarcinoma of the Prostate?: An Immunohistochemical Study Using High Molecular Weight Cytokeratin (Clone 34&bgr;E12) Antibody , 2002, The American journal of surgical pathology.

[2]  G. Mohapatra,et al.  Tumor necrosis in radical prostatectomies with high-grade prostate cancer is associated with multiple poor prognostic features and a high prevalence of residual disease. , 2017, Human pathology.

[3]  Daan Nieboer,et al.  Gleason grade 4 prostate adenocarcinoma patterns: an interobserver agreement study among genitourinary pathologists , 2016, Histopathology.

[4]  P. Carroll,et al.  Expansile cribriform Gleason pattern 4 has histopathologic and molecular features of aggressiveness and greater risk of biochemical failure compared to glomerulation Gleason pattern 4 , 2020, The Prostate.

[5]  Esther I Verhoef,et al.  Prostate cancer outcomes of men with biopsy Gleason score 6 and 7 without cribriform or intraductal carcinoma. , 2016, European journal of cancer.

[6]  J. McKenney,et al.  Impact of Cribriform Pattern and Intraductal Carcinoma on Gleason 7 Prostate Cancer Treated with External Beam Radiotherapy. , 2019, The Journal of urology.

[7]  C. Morash,et al.  Cribriform morphology predicts upstaging after radical prostatectomy in patients with Gleason score 3 + 4 = 7 prostate cancer at transrectal ultrasound (TRUS)-guided needle biopsy , 2015, Virchows Archiv.

[8]  S. Dhanasekaran,et al.  The long noncoding RNA SChLAP1 promotes aggressive prostate cancer and antagonizes the SWI/SNF complex , 2013, Nature Genetics.

[9]  W. V. van Cappellen,et al.  Three-dimensional analysis reveals two major architectural subgroups of prostate cancer growth patterns , 2019, Modern Pathology.

[10]  J. Epstein,et al.  Gleason grading of prostatic adenocarcinoma with glomeruloid features on needle biopsy. , 2009, Human pathology.

[11]  M. Cooperberg,et al.  Genomic Markers in Prostate Cancer Decision Making. , 2018, European urology.

[12]  Bing Zhang,et al.  Combined clinical characteristics and multiparametric MRI parameters for prediction of cribriform morphology in intermediate-risk prostate cancer patients. , 2020, Urologic oncology.

[13]  J. McKenney,et al.  Diagnostic Accuracy of Prostate Biopsy for Detecting Cribriform Gleason Pattern 4 Carcinoma and Intraductal Carcinoma in Paired Radical Prostatectomy Specimens: Implications for Active Surveillance. , 2020, The Journal of urology.

[14]  Andrew J Ewald,et al.  Morphogenesis of epithelial tubes: Insights into tube formation, elongation, and elaboration. , 2010, Developmental biology.

[15]  J. McKenney The present and future of prostate cancer histopathology , 2017, Current opinion in urology.

[16]  J. Epstein,et al.  Intraductal carcinoma of the prostate on needle biopsy: histologic features and clinical significance , 2006, Modern Pathology.

[17]  T. Tsuzuki,et al.  Propensity score‐matched comparison of docetaxel and androgen receptor axis‐targeted agents in patients with castration‐resistant intraductal carcinoma of the prostate , 2019, BJU international.

[18]  R. Henrique,et al.  Relative copy number gain of MYC in diagnostic needle biopsies is an independent prognostic factor for prostate cancer patients. , 2007, European urology.

[19]  M. Loda,et al.  Genetic and Epigenetic Determinants of Aggressiveness in Cribriform Carcinoma of the Prostate , 2018, Molecular Cancer Research.

[20]  Toyonori Tsuzuki,et al.  Diagnosis of “Poorly Formed Glands” Gleason Pattern 4 Prostatic Adenocarcinoma on Needle Biopsy: An Interobserver Reproducibility Study Among Urologic Pathologists With Recommendations , 2015, The American journal of surgical pathology.

[21]  J. Epstein,et al.  Differential Diagnosis of Intraductal Lesions of the Prostate , 2016, The American journal of surgical pathology.

[22]  A. Chinnaiyan,et al.  Correlation between cribriform/intraductal prostatic adenocarcinoma and percent Gleason pattern 4 to a 22-gene genomic classifier. , 2019, The Prostate.

[23]  Lawrence D. True,et al.  The critical role of the pathologist in determining eligibility for active surveillance as a management option in patients with prostate cancer: consensus statement with recommendations supported by the College of American Pathologists, International Society of Urological Pathology, Association of D , 2014, Archives of pathology & laboratory medicine.

[24]  Adam K Glaser,et al.  Open-Top Light-Sheet Microscopy Image Atlas of Prostate Core Needle Biopsies. , 2019, Archives of pathology & laboratory medicine.

[25]  J. Cheville,et al.  Reporting Practices and Resource Utilization in the Era of Intraductal Carcinoma of the Prostate , 2019, The American journal of surgical pathology.

[26]  Ping Yang,et al.  Architectural Heterogeneity and Cribriform Pattern Predict Adverse Clinical Outcome for Gleason Grade 4 Prostatic Adenocarcinoma , 2013, The American journal of surgical pathology.

[27]  T. Tsuzuki,et al.  Prognostic value of intraductal carcinoma of the prostate in radical prostatectomy specimens , 2014, The Prostate.

[28]  C. Morash,et al.  Evaluation of tumor morphologies and association with biochemical recurrence after radical prostatectomy in grade group 5 prostate cancer , 2018, Virchows Archiv.

[29]  G. Kristiansen Markers of clinical utility in the differential diagnosis and prognosis of prostate cancer , 2018, Modern Pathology.

[30]  G. Jenster,et al.  Novel long non-coding RNAs are specific diagnostic and prognostic markers for prostate cancer , 2015, Oncotarget.

[31]  A. Houtsmuller,et al.  Three‐dimensional microscopic analysis of clinical prostate specimens , 2016, Histopathology.

[32]  E. Messing,et al.  Historical and contemporary perspectives on cribriform morphology in prostate cancer , 2018, Nature Reviews Urology.

[33]  A. Evans,et al.  Active surveillance for the management of localized prostate cancer: Guideline recommendations. , 2015, Canadian Urological Association journal = Journal de l'Association des urologues du Canada.

[34]  L. Egevad,et al.  The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma , 2005, The American journal of surgical pathology.

[35]  Ewout W Steyerberg,et al.  Cribriform growth is highly predictive for postoperative metastasis and disease-specific death in Gleason score 7 prostate cancer , 2015, Modern Pathology.

[36]  Y. Bao,et al.  The Prognostic Value of the Proportion and Architectural Patterns of Intraductal Carcinoma of the Prostate in Patients with De Novo Metastatic Prostate Cancer , 2019, The Journal of urology.

[37]  J. Epstein,et al.  Interobserver reproducibility of Gleason grading of prostatic carcinoma: general pathologist. , 2001, Human pathology.

[38]  Ladan Fazli,et al.  The potential impact of reproducibility of Gleason grading in men with early stage prostate cancer managed by active surveillance: a multi-institutional study. , 2011, The Journal of urology.

[39]  G. Kristiansen,et al.  Three‐dimensional reconstruction of prostate cancer architecture with serial immunohistochemical sections: hallmarks of tumour growth, tumour compartmentalisation, and implications for grading and heterogeneity , 2018, Histopathology.

[40]  Hiroyuki Takahashi,et al.  Cases Having a Gleason Score 3+4=7 With <5% of Gleason Pattern 4 in Prostate Needle Biopsy Show Similar Failure-free Survival and Adverse Pathology Prevalence to Gleason Score 6 Cases in a Radical Prostatectomy Cohort , 2019, The American journal of surgical pathology.

[41]  A. Evans,et al.  Role of Magnetic Resonance Imaging Targeted Biopsy in Detection of Prostate Cancer Harboring Adverse Pathological Features of Intraductal Carcinoma and Invasive Cribriform Carcinoma , 2018, The Journal of urology.

[42]  Jennifer R. Rider,et al.  A Prospective Investigation of PTEN Loss and ERG Expression in Lethal Prostate Cancer. , 2015, Journal of the National Cancer Institute.

[43]  Ziding Feng,et al.  Histologic Grading of Prostatic Adenocarcinoma Can Be Further Optimized: Analysis of the Relative Prognostic Strength of Individual Architectural Patterns in 1275 Patients From the Canary Retrospective Cohort , 2016, The American journal of surgical pathology.

[44]  A. Zlotta,et al.  The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Glea- son Grading of Prostatic Carcinoma , 2006 .

[45]  A. Mes-Masson,et al.  Risk stratification of prostate cancer through quantitative assessment of PTEN loss (qPTEN). , 2020, Journal of the National Cancer Institute.

[46]  C. Morash,et al.  Utility of Gleason pattern 4 morphologies detected on transrectal ultrasound (TRUS)-guided biopsies for prediction of upgrading or upstaging in Gleason score 3 + 4 = 7 prostate cancer , 2016, Virchows Archiv.

[47]  K. Iczkowski,et al.  The 2019 International Society of Urological Pathology (ISUP) Consensus Conference on Grading of Prostatic Carcinoma. , 2021, The American journal of surgical pathology.

[48]  S. Prendeville,et al.  Grading of prostate cancer: the impact of including intraductal carcinoma on the overall Grade Group assigned in diagnostic biopsies , 2020, Histopathology.

[49]  M J Miller,et al.  Three-dimensional microscopic image reconstruction of prostatic adenocarcinoma. , 2001, Archives of pathology & laboratory medicine.

[50]  T. H. van der Kwast,et al.  Improved Prostate Cancer Biopsy Grading by Incorporation of Invasive Cribriform and Intraductal Carcinoma in the 2014 Grade Groups. , 2020, European urology.

[51]  A. Haese*,et al.  Clinical Utility of Quantitative Gleason Grading in Prostate Biopsies and Prostatectomy Specimens. , 2016, European urology.

[52]  G. V. van Leenders,et al.  Morphological and immunohistochemical identification of epithelial-to-mesenchymal transition in clinical prostate cancer , 2015, Oncotarget.

[53]  G. Litjens,et al.  The 2019 International Society of Urological Pathology (ISUP) Consensus Conference on Grading of Prostatic Carcinoma , 2020, The American journal of surgical pathology.

[54]  J. Epstein,et al.  Gleason Pattern 4 with Cribriform Morphology on Biopsy is Associated with Adverse Clinicopathological Findings in a Prospective Radical Prostatectomy Cohort. , 2020, Human pathology.

[55]  Wei Huang,et al.  Digital quantification of five high-grade prostate cancer patterns, including the cribriform pattern, and their association with adverse outcome. , 2011, American journal of clinical pathology.

[56]  D. Berney,et al.  Standardization of Gleason grading among 337 European pathologists , 2013, Histopathology.

[57]  T. H. van der Kwast,et al.  A Prostate Cancer "Nimbosus": Genomic Instability and SChLAP1 Dysregulation Underpin Aggression of Intraductal and Cribriform Subpathologies. , 2017, European urology.

[58]  D. Nieboer,et al.  Presence of invasive cribriform or intraductal growth at biopsy outperforms percentage grade 4 in predicting outcome of Gleason score 3+4=7 prostate cancer , 2017, Modern Pathology.

[59]  M. Roobol,et al.  Concordance of cribriform architecture in matched prostate cancer biopsy and radical prostatectomy specimens , 2019, Histopathology.

[60]  T. H. van der Kwast,et al.  Biopsy diagnosis of intraductal carcinoma is prognostic in intermediate and high risk prostate cancer patients treated by radiotherapy. , 2012, European journal of cancer.

[61]  P. Zhang,et al.  The prognostic implication of intraductal carcinoma of the prostate in metastatic castration-resistant prostate cancer and its potential predictive value in those treated with docetaxel or abiraterone as first-line therapy. , 2017, Oncotarget.

[62]  B. Delahunt,et al.  The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System , 2015, The American journal of surgical pathology.

[63]  T. Tsuzuki,et al.  Efficacy of docetaxel in castration-resistant prostate cancer patients with intraductal carcinoma of the prostate , 2018, International Journal of Clinical Oncology.

[64]  John T. Wei,et al.  Association of ERG/PTEN status with biochemical recurrence after radical prostatectomy for clinically localized prostate cancer , 2018, Medical Oncology.

[65]  H. G. van der Poel,et al.  Clinicopathological characteristics of glomeruloid architecture in prostate cancer , 2020, Modern Pathology.

[66]  R. Shah,et al.  Atypical Cribriform Lesions of the Prostate: Clinical Significance, Differential Diagnosis and Current Concept of Intraductal Carcinoma of the Prostate , 2012, Advances in anatomic pathology.

[67]  A. Evans,et al.  Concordance of biopsy and prostatectomy diagnosis of intraductal and cribriform carcinoma in a prospectively collected data set , 2018, Histopathology.

[68]  Lawrence D. True,et al.  Multi-immersion open-top light-sheet microscope for high-throughput imaging of cleared tissues , 2019, Nature Communications.

[69]  J. Ro,et al.  Spectrum of Cribriform Proliferations of the Prostate: From Benign to Malignant. , 2018, Archives of pathology & laboratory medicine.

[70]  D. Bostwick,et al.  Detection of chromosomal anomalies and c-myc gene amplification in the cribriform pattern of prostatic intraepithelial neoplasia and carcinoma by fluorescence in situ hybridization. , 1997, Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc.

[71]  Andrew J. Evans,et al.  Interactive digital slides with heat maps: a novel method to improve the reproducibility of Gleason grading , 2011, Virchows Archiv.

[72]  Esther I Verhoef,et al.  Disease-specific survival of patients with invasive cribriform and intraductal prostate cancer at diagnostic biopsy , 2016, Modern Pathology.

[73]  A. Shalhav,et al.  Prognostic Significance of Percentage and Architectural Types of Contemporary Gleason Pattern 4 Prostate Cancer in Radical Prostatectomy , 2016, The American journal of surgical pathology.

[74]  T. H. van der Kwast,et al.  Intraductal carcinoma has a minimal impact on Grade Group assignment in prostate cancer biopsy and radical prostatectomy specimens , 2020, Histopathology.

[75]  Esther I Verhoef,et al.  Large cribriform growth pattern identifies ISUP grade 2 prostate cancer at high risk for recurrence and metastasis , 2018, Modern Pathology.

[76]  T. H. van der Kwast,et al.  Prognostic impact of intraductal carcinoma and large cribriform carcinoma architecture after prostatectomy in a contemporary cohort. , 2014, European journal of cancer.

[77]  M. Roobol,et al.  Clinical outcome comparison of Grade Group 1 and Grade Group 2 prostate cancer with and without cribriform architecture at the time of radical prostatectomy , 2020, Histopathology.

[78]  B. Sarbay,et al.  The association of the cribriform pattern with outcome for prostatic adenocarcinomas. , 2014, Pathology, research and practice.

[79]  P. Carroll,et al.  Correlation of a Commercial Genomic Risk Classifier with Histological Patterns in Prostate Cancer. , 2019, The Journal of urology.

[80]  J. Epstein,et al.  Gleason score 7 adenocarcinoma of the prostate with lymph node metastases: analysis of 184 radical prostatectomy specimens. , 2013, Archives of pathology & laboratory medicine.

[81]  J. Lindberg,et al.  Genetic markers associated with early cancer‐specific mortality following prostatectomy , 2013, Cancer.

[82]  K. Iczkowski,et al.  PTEN loss and p27 loss differ among morphologic patterns of prostate cancer, including cribriform. , 2017, Human pathology.

[83]  K. Iczkowski,et al.  Outcome of Gleason 3 + 5 = 8 Prostate Cancer Diagnosed on Needle Biopsy: Prognostic Comparison with Gleason 4 + 4 = 8. , 2016, The Journal of urology.

[84]  Takafumi N. Yamaguchi,et al.  Cribriform and intraductal prostate cancer are associated with increased genomic instability and distinct genomic alterations , 2018, BMC Cancer.

[85]  Ximing J. Yang,et al.  The 2019 Genitourinary Pathology Society (GUPS) White Paper on Contemporary Grading of Prostate Cancer. , 2020, Archives of pathology & laboratory medicine.

[86]  J. Squire,et al.  Recurrent copy number alterations in prostate cancer: an in silico meta-analysis of publicly available genomic data. , 2014, Cancer genetics.