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Basic & translational oncology MolMed, Rotterdam Oct 9, 2018 What every scientist should know about pathology: lessons from the prostate Arno van Leenders Pathology Erasmus MC, Rotterdam The Prostate 1 cm The Prostate 1. Description


  1. Basic & translational oncology MolMed, Rotterdam Oct 9, 2018 What every scientist should know about pathology: lessons from the prostate Arno van Leenders Pathology Erasmus MC, Rotterdam

  2. The Prostate 1 cm

  3. The Prostate 1. Description 2. Ink margins 3. Freeze for research

  4. 90% 60% Frozen and FFPE samples 5% are very heterogeneous

  5. Pathological assessment • Gleason score • pT-stage (extra-prostatic growth) • Surgical margin • Lymph node metastasis

  6. Gleason grading system  1966 - 2016: 50 th anniversary  Based on tumor growth patterns  Accounts for tumor heterogeneity  Modifications in 2005 and 2016

  7. Normal Gleason 3

  8. Gleason 4 Gleason 5

  9. Gleason score Accounts for heterogeneity: adding 2 most common patterns Gleason 3 Gleason 4 Gleason score: 3 + 4 = 7

  10. Gleason score 6 does not cause PCa death 3+3=6 3+4=7 4+3=7 >7 n = 1101

  11. Gleason score 3+4=7 on biopsy “The 2 most common patterns ” G3 55% G4 45% Gleason score 3+4=7 G3 99% G4 1%

  12. Quantification of Grade 4 component BCRFS after radical prostatectomy G4 % in GS 7 6 6 5% 7 (3+4) 6-10% 7 (3+4) 11-20% 7 (3+4) 21-30% 7 (4+3) 31-49% 8 7 (4+3) 50-60% 9-10 61-80% 7 (4+3) 8 >80% 9-10 Sauter Eur Urol 2016

  13. GG 5 κ fused GG 4 ill-formed κ glomeruloid GG 3 cribriform

  14. Frequency Gleason grade 4 patterns Ill-defined 66% One pattern 22% Fused 76% Two patterns 47% Glomeruloid 28% Three patterns 26% Cribriform 38% Four patterns 5%

  15. Cribriform GS 7 at radical prostatectomy without cribriform with cribriform

  16. Cribriform GS 7 at biopsy

  17. Cribriform GS 7 at biopsy

  18. Cribriform GS 7 at biopsy: BCRFS

  19. Cribriform growth and % GG4 are related Parameter Percentage Gleason grade 4 P-value 0-10% 10-25% 25-50% Number 121 131 118 Age 65 (66; 61-70) 67 (68; 63-72) 68 (69; 65-72) .001 PSA (ng/mL) 7.8 (5.2; 3.7-7.1) 9.2 (5.9; 4.2-9.0) 11.7 (8.5; 5.4-13.4) <.001 % positive biopsies 51 (50; 33-67) 44 (43; 29-57) 48 (43; 29-67) .01 % tumor volume 39 (37; 25-52) 44 (45; 27-59) 50 (51; 34-65) .001 CR/IDC 7 (6%) 29 (22%) 52 (44%) <.001 Disease-specific death 4 (3%) 6 (5%) 13 (11%) .02

  20. Biomarkers for risk stratification Commercially available, standardized tests Commercial test Based Specimen Outcome Decipher 22 genes RP metastasis Oncotype DX 12 genes PBx, RP adverse PA at RP, BCR, metastasis Prolaris 31 genes PBx, RP BCR, DFS ProMark 8 genes PBx adverse PA at RP Validated in several studies Additive value to existing nomograms

  21. Biomarker test versus pathology 2018? No information on % GG4 Invasive and intraductal carcinoma not considered Sampling artefact? Increased use of multiparametric MRI Additional value in contemporary cohorts to be determined

  22. “Easy” biomarkers in prostate cancer Potential value for Ki67, p27, EZH2, c- MYC, PTEN, … Different antibodies, platforms, cut-offs, endpoints , … Subjective scoring “ eye balling” No additional value in prostate cancer stratification

  23. Molecular biology of GS 3+4=7? HE DNA/RNA Growth patterns 3+4=7 3 4 cr 3 3 4 ill Genomic black box

  24. Genomic instability in cribriform growth + + CR - - + - - - + GS 6 3+4 4+3 8 9-10 Chua, Eur Urol 2017; Böttcher, Submitted

  25. GG4 cribriform: progressive genomic loss GG3 Cribriform GG4

  26. Molecular background GG4 cribriform CISH c-MY C in 20 prostate cancer specimens 500 cells counted (amplification if mean > 2.2)

  27. GG4 ill-defined: EMT/Cadherin switching N-Cadherin ill-defined GG4 Kolijn, Oncotarget 2015

  28. Microscopic evolution … ? 1674 2016

  29. Histopathologic delineation ? ? ? ? Gleason grade 3

  30. x y 800 µ m z GG 4 ill-formed BABB clearing Before After

  31. GG 3 glandular GG 4 ill-formed GG 4 cribriform

  32. Take home messages  Gain basic knowledge of pathology  Far more to say, than PA report only  Contact your pathologist at early stage

  33. Thank you! Rotterdam, NL Chris Bangma Rene Böttcher Guido Jenster Charlotte Kweldam Daan Nieboer Monique Roobol Martin van Royen Ewout Steyerberg Esther Verhoef Toronto, CA Paul Boutros Rob Bristow Michael Fraser Theo van der Kwast g.vanleenders@erasmusmc.nl

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