A Multi-Institutional Validation of Gleason Score Derived from Tissue Microarray Cores

  • Sami-Ramzi Leyh-Bannurah
  • Dominique Trudel
  • Mathieu Latour
  • Emanuele Zaffuto
  • Andree-Anne Grosset
  • Christine Tam
  • Veronique Ouellet
  • Markus Graefen
  • Lars Budäus
  • Armen G. Aprikian
  • Louis Lacombe
  • Neil E. Fleshner
  • Martin E. Gleave
  • Anne-Marie Mes-Masson
  • Fred Saad
  • Pierre I Karakiewicz
Original Article


To test the agreement between high-grade PCa at RP and TMA, and the ability of TMA to predict BCR. Validation of concordance between tissue microarray (TMA) and radical prostatectomy (RP) high-grade prostate cancer (PCa) is crucial because latter determines the treated natural history of PCa. We hypothesized that TMA Gleason score is in agreement with RP pathology and capable of accurately predicting biochemical recurrence (BCR). Data were provided from a multi-institutional Canadian sample of 1333 TMA and RP specimens with complete clinicopathological data. First, rate of agreement between TMA and high-grade Gleason at RP or biopsy and RP was tested. Second, ability of RP, TMA and biopsy to predict BCR was compared. Multivariable (MVA) Cox regression models were fitted and BCR rates were illustrated with Kaplan-Meier plots. Agreement between RP and TMA and between RP and biopsy was 72.6% (95% CI:69.7–75.5) and 60.4% (95% CI:57.2–63.6), respectively. In MVA predicting BCR, the accuracy for RP, TMA and biopsy was 0.73, 0.72 and 0.68, respectively. TMA added discriminatory ability among exclusively low-grade Gleason RP patients (p = 0.02), but did not improve BCR discrimination in exclusive high-grade PCa RP patients (p = 0.8). TMA Gleason grade accurately reflects presence of high-grade Gleason in RP specimen, accurately predicts BCR rates after RP and improves prediction of BCR in low-grade Gleason patients at RP.


Radical prostatectomy Prostate cancer Gleason grade agreement Biochemical recurrence Validation 



The Network acknowledges contributions to its CPCBN biobank from several Institutions across Canada, namely Centre hospitalier de l’Université de Montreal (CHUM), Centre hospitalier universitaire de Quebec (CHUQ), McGill University Health Centre (MUHC), University Health Network (UHN), University of British Columbia/Vancouver Coastal Health Authority.

Authors’ Contribution

All authors of this research paper have directly participated in the planning, execution, or analysis of the study. All authors of this paper have read and approved the final version submitted. The authors listed below have made substantial contributions to the intellectual content of the paper in the various sections described below:

SR Leyh-Bannurah: data analysis, data management, manuscript writing.

D Trudel: data analysis, protocol development, manuscript writing.

M Latour: project development, manuscript editing.

E Zaffuto: manuscript editing, data analysis.

AA Grosset: manuscript editing, data collection.

C Tam: protocol development, project development, data collection.

V Ouellet: protocol development, project development, manuscript editing.

M Graefen: manuscript editing, data analysis.

L Budäus: manuscript editing, manuscript editing.

A Aprikian: project development, data analysis.

L Lacombe: project development, data analysis.

N Fleshner: data analysis, protocol development, manuscript editing.

ME Gleave: protocol development, data collection.

AM Mes-Masson: protocol development, data collection.

F Saad: project development, data collection, data management, manuscript editing.

PI Karakiewicz: project development, data analysis, manuscript writing, manuscript editing.

Compliance with Ethical Standards

Conflict of Interest

There are no conflicts of interest. The contents of this manuscript have not been copyrighted or published previously. The contents of this manuscript are not under consideration for publication elsewhere.

Ethical Standars

Informed written consent was obtained and ethical standards were adhered to.

Supplementary material

12253_2018_408_MOESM1_ESM.docx (13 kb)
ESM 1 (DOCX 12 kb)


  1. 1.
    Santoni M, Scarpelli M, Mazzucchelli R, Lopez-Beltran A, Cheng L, Epstein JI, Cascinu S, Briganti A, Catto JW, Montorsi F, Montironi R (2016) Current Histopathologic and molecular Characterisations of prostate Cancer: towards individualised prognosis and therapies. European Urology 69(2):186–190. CrossRefPubMedGoogle Scholar
  2. 2.
    Wittschieber D, Kollermann J, Schlomm T, Sauter G, Erbersdobler A (2010) Nuclear grading versus Gleason grading in small samples containing prostate cancer: a tissue microarray study. Pathology oncology research: POR 16(4):479–484. CrossRefPubMedGoogle Scholar
  3. 3.
    Epstein JI, Zelefsky MJ, Sjoberg DD, Nelson JB, Egevad L, Magi-Galluzzi C, Vickers AJ, Parwani AV, Reuter VE, Fine SW, Eastham JA, Wiklund P, Han M, Reddy CA, Ciezki JP, Nyberg T, Klein EA (2016) A contemporary prostate Cancer grading system: a validated alternative to the Gleason score. European Urology 69(3):428–435. CrossRefPubMedGoogle Scholar
  4. 4.
    Loeb S, Folkvaljon Y, Robinson D, Lissbrant IF, Egevad L, Stattin P (2015) Evaluation of the 2015 Gleason grade groups in a Nationwide population-based cohort. European Urology 69:1135–1141. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Sauter G, Steurer S, Clauditz TS, Krech T, Wittmer C, Lutz F, Lennartz M, Janssen T, Hakimi N, Simon R, von Petersdorff-Campen M, Jacobsen F, von Loga K, Wilczak W, Minner S, Tsourlakis MC, Chirico V, Haese A, Heinzer H, Beyer B, Graefen M, Michl U, Salomon G, Steuber T, Budaus LH, Hekeler E, Malsy-Mink J, Kutzera S, Fraune C, Gobel C, Huland H, Schlomm T (2016) Clinical utility of quantitative Gleason grading in prostate biopsies and prostatectomy specimens. European Urology 69(4):592–598. CrossRefPubMedGoogle Scholar
  6. 6.
    Timilshina N, Ouellet V, Alibhai SM, Mes-Masson AM, Delvoye N, Drachenberg D, Finelli A, Jammal MP, Karakiewicz P, Lapointe H, Lattouf JB, Lynch K, Paradis JB, Sitarik P, So A, Saad F (2016) Analysis of active surveillance uptake for low-risk localized prostate cancer in Canada: a Canadian multi-institutional study. World Journal of Urology 35:595–603. CrossRefPubMedGoogle Scholar
  7. 7.
    Meyer CP, Hansen J, Boehm K, Tilki D, Abdollah F, Trinh QD, Fisch M, Sauter G, Graefen M, Huland H, Chun FK, Ahyai SA (2016) Tumor volume improves the long-term prediction of biochemical recurrence-free survival after radical prostatectomy for localized prostate cancer with positive surgical margins. World Journal of Urology 35:199–206. CrossRefPubMedGoogle Scholar
  8. 8.
    Budaus L, Isbarn H, Eichelberg C, Lughezzani G, Sun M, Perrotte P, Chun FK, Salomon G, Steuber T, Kollermann J, Sauter G, Ahyai SA, Zacharias M, Fisch M, Schlomm T, Haese A, Heinzer H, Huland H, Montorsi F, Graefen M, Karakiewicz PI (2010) Biochemical recurrence after radical prostatectomy: multiplicative interaction between surgical margin status and pathological stage. The Journal of Urology 184(4):1341–1346. CrossRefPubMedGoogle Scholar
  9. 9.
    Isbarn H, Ahyai SA, Chun FK, Budaus L, Schlomm T, Salomon G, Zacharias M, Erbersdobler A, Kollermann J, Sauter G, Huland H, Graefen M, Steuber T (2009) Prevalence of a tertiary Gleason grade and its impact on adverse histopathologic parameters in a contemporary radical prostatectomy series. European Urology 55(2):394–401. CrossRefPubMedGoogle Scholar
  10. 10.
    Suardi N, Porter CR, Reuther AM, Walz J, Kodama K, Gibbons RP, Correa R, Montorsi F, Graefen M, Huland H, Klein EA, Karakiewicz PI (2008) A nomogram predicting long-term biochemical recurrence after radical prostatectomy. Cancer 112(6):1254–1263. CrossRefPubMedGoogle Scholar
  11. 11.
    Briganti A, Karnes RJ, Joniau S, Boorjian SA, Cozzarini C, Gandaglia G, Hinkelbein W, Haustermans K, Tombal B, Shariat S, Sun M, Karakiewicz PI, Montorsi F, Van Poppel H, Wiegel T (2014) Prediction of outcome following early salvage radiotherapy among patients with biochemical recurrence after radical prostatectomy. European Urology 66(3):479–486. CrossRefPubMedGoogle Scholar
  12. 12.
    Lughezzani G, Briganti A, Karakiewicz PI, Kattan MW, Montorsi F, Shariat SF, Vickers AJ (2010) Predictive and prognostic models in radical prostatectomy candidates: a critical analysis of the literature. European Urology 58(5):687–700. CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Lughezzani G, Budaus L, Isbarn H, Sun M, Perrotte P, Haese A, Chun FK, Schlomm T, Steuber T, Heinzer H, Huland H, Montorsi F, Graefen M, Karakiewicz PI (2010) Head-to-head comparison of the three most commonly used preoperative models for prediction of biochemical recurrence after radical prostatectomy. European Urology 57(4):562–568. CrossRefPubMedGoogle Scholar
  14. 14.
    Walz J, Chun FK, Klein EA, Reuther A, Saad F, Graefen M, Huland H, Karakiewicz PI (2009) Nomogram predicting the probability of early recurrence after radical prostatectomy for prostate cancer. The Journal of Urology 181(2):601–607; discussion 607-608. CrossRefPubMedGoogle Scholar
  15. 15.
    Epstein JI, Egevad L, Amin MB, Delahunt B, Srigley JR, Humphrey PA, Grading C (2016) 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. The American Journal of Surgical Pathology 40(2):244–252. PubMedGoogle Scholar
  16. 16.
    Bubendorf L, Nocito A, Moch H, Sauter G (2001) Tissue microarray (TMA) technology: miniaturized pathology archives for high-throughput in situ studies. The Journal of Pathology 195(1):72–79. CrossRefPubMedGoogle Scholar
  17. 17.
    Rubin MA, Dunn R, Strawderman M, Pienta KJ (2002) Tissue microarray sampling strategy for prostate Cancer biomarker analysis. The American Journal of Surgical Pathology 26(3):312–319. CrossRefPubMedGoogle Scholar
  18. 18.
    Diallo JS, Aldejmah A, Mouhim AF, Fahmy MA, Koumakpayi IH, Sircar K, Begin LR, Mes-Masson AM, Saad F (2008) Co-assessment of cytoplasmic and nuclear androgen receptor location in prostate specimens: potential implications for prostate cancer development and prognosis. BJU International 101(10):1302–1309. CrossRefPubMedGoogle Scholar
  19. 19.
    Gannon PO, Lessard L, Stevens LM, Forest V, Begin LR, Minner S, Tennstedt P, Schlomm T, Mes-Masson AM, Saad F (2013) Large-scale independent validation of the nuclear factor-kappa B p65 prognostic biomarker in prostate cancer. European Journal of Cancer 49(10):2441–2448. CrossRefPubMedGoogle Scholar
  20. 20.
    Koumakpayi IH, Le Page C, Mes-Masson AM, Saad F (2010) Hierarchical clustering of immunohistochemical analysis of the activated ErbB/PI3K/Akt/NF-kappaB signalling pathway and prognostic significance in prostate cancer. British Journal of Cancer 102(7):1163–1173. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Ross AE, Johnson MH, Yousefi K, Davicioni E, Netto GJ, Marchionni L, Fedor HL, Glavaris S, Choeurng V, Buerki C, Erho N, Lam LL, Humphreys EB, Faraj S, Bezerra SM, Han M, Partin AW, Trock BJ, Schaeffer EM (2016) Tissue-based genomics augments post-prostatectomy risk stratification in a natural history cohort of intermediate- and high-risk men. European Urology 69(1):157–165. CrossRefPubMedGoogle Scholar
  22. 22.
    Ruela-de-Sousa RR, Hoekstra E, Hoogland AM, Souza Queiroz KC, Peppelenbosch MP, Stubbs AP, Pelizzaro-Rocha K, van Leenders GJ, Jenster G, Aoyama H, Ferreira CV, Fuhler GM (2016) Low-molecular-weight protein tyrosine phosphatase predicts prostate Cancer outcome by increasing the metastatic potential. European Urology 69(4):710–719. CrossRefPubMedGoogle Scholar
  23. 23.
    Belledant A, Hovington H, Garcia L, Caron P, Brisson H, Villeneuve L, Simonyan D, Tetu B, Fradet Y, Lacombe L, Guillemette C, Levesque E (2016) The UGT2B28 sex-steroid inactivation pathway is a regulator of Steroidogenesis and modifies the risk of prostate Cancer progression. European Urology 69(4):601–609. CrossRefPubMedGoogle Scholar
  24. 24.
    Bostrom PJ, Bjartell AS, Catto JW, Eggener SE, Lilja H, Loeb S, Schalken J, Schlomm T, Cooperberg MR (2015) Genomic predictors of outcome in prostate Cancer. European Urology 68:1033–1044. CrossRefPubMedGoogle Scholar
  25. 25.
    Cullen J, Rosner IL, Brand TC, Zhang N, Tsiatis AC, Moncur J, Ali A, Chen Y, Knezevic D, Maddala T, Lawrence HJ, Febbo PG, Srivastava S, Sesterhenn IA, McLeod DG (2015) A biopsy-based 17-gene genomic prostate score predicts recurrence after radical prostatectomy and adverse surgical pathology in a racially diverse population of men with clinically low- and intermediate-risk prostate Cancer. European Urology 68(1):123–131. CrossRefPubMedGoogle Scholar
  26. 26.
    Eggener S (2015) Prostate Cancer screening biomarkers: an emerging embarrassment of 'Riches'? European Urology 70:54–55. CrossRefPubMedGoogle Scholar
  27. 27.
    Schlomm T, Weischenfeldt J, Korbel J, Sauter G (2015) The aging prostate is never "normal": implications from the genomic characterization of multifocal prostate cancers. European Urology 68:348–350. CrossRefPubMedGoogle Scholar
  28. 28.
    Klein EA, Yousefi K, Haddad Z, Choeurng V, Buerki C, Stephenson AJ, Li J, Kattan MW, Magi-Galluzzi C, Davicioni E (2015) A genomic classifier improves prediction of metastatic disease within 5 years after surgery in node-negative high-risk prostate cancer patients managed by radical prostatectomy without adjuvant therapy. European Urology 67(4):778–786. CrossRefPubMedGoogle Scholar
  29. 29.
    Tomlins SA, Day JR, Lonigro RJ, Hovelson DH, Siddiqui J, Kunju LP, Dunn RL, Meyer S, Hodge P, Groskopf J, Wei JT, Chinnaiyan AM (2015) Urine TMPRSS2:ERG plus PCA3 for individualized prostate Cancer risk assessment. European Urology 70:45–53. CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Mehra R, Udager AM, Ahearn TU, Cao X, Feng FY, Loda M, Petimar JS, Kantoff P, Mucci LA, Chinnaiyan AM (2015) Overexpression of the long non-coding RNA SChLAP1 independently predicts lethal prostate Cancer. European Urology 70:549–552. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Rubin MA, Girelli G, Demichelis F (2016) Genomic correlates to the newly proposed grading prognostic groups for prostate Cancer. European Urology 69(4):557–560. CrossRefPubMedGoogle Scholar
  32. 32.
    Chun FK, Briganti A, Graefen M, Montorsi F, Porter C, Scattoni V, Gallina A, Walz J, Haese A, Steuber T, Erbersdobler A, Schlomm T, Ahyai SA, Currlin E, Valiquette L, Heinzer H, Rigatti P, Huland H, Karakiewicz PI (2007) Development and external validation of an extended 10-core biopsy nomogram. European Urology 52(2):436–444. CrossRefPubMedGoogle Scholar
  33. 33.
    Siddiqui MM, Rais-Bahrami S, Turkbey B, George AK, Rothwax J, Shakir N, Okoro C, Raskolnikov D, Parnes HL, Linehan WM (2015) Comparison of MR/ultrasound fusion–guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. JAMA 313(4):390–397CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2018

Authors and Affiliations

  • Sami-Ramzi Leyh-Bannurah
    • 1
    • 2
  • Dominique Trudel
    • 3
    • 4
  • Mathieu Latour
    • 3
    • 4
  • Emanuele Zaffuto
    • 1
    • 6
  • Andree-Anne Grosset
    • 7
  • Christine Tam
    • 7
  • Veronique Ouellet
    • 7
  • Markus Graefen
    • 2
  • Lars Budäus
    • 2
  • Armen G. Aprikian
    • 8
  • Louis Lacombe
    • 9
  • Neil E. Fleshner
    • 10
  • Martin E. Gleave
    • 11
  • Anne-Marie Mes-Masson
    • 4
    • 7
  • Fred Saad
    • 5
    • 7
  • Pierre I Karakiewicz
    • 1
    • 5
  1. 1.Cancer Prognostics and Health Outcomes UnitUniversity of Montreal Health CenterMontrealCanada
  2. 2.Martini-Clinic, Prostate Cancer Center Hamburg-EppendorfHamburgGermany
  3. 3.Department of Pathology and Cellular BiologyUniversité de MontréalMontrealCanada
  4. 4.Department of MedecineUniversité de MontréalMontrealCanada
  5. 5.Department of SurgeryUniversité de MontréalMontrealCanada
  6. 6.Department of Urology and Division of Experimental OncologyURI, Urological Research Institute, IRCCS San Raffaele Scientific InstituteMilanItaly
  7. 7.Institut du Cancer de Montreal and Centre de recherche du centre hospitalier de l’Université de MontréalQCCanada
  8. 8.Research Institute of McGill University Health Center and Department of Surgery (Urology)McGill UniversityQCCanada
  9. 9.CHU de QuébecQuebecCanada
  10. 10.Division of Urology, Department of SurgeryUniversity Health Network, University of TorontoTorontoCanada
  11. 11.Vancouver Prostate Centre & Department of Urologic ScienceUniversity of British ColumbiaVancouverCanada

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