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What every scientist should know about pathology: lessons from the - - PowerPoint PPT Presentation
What every scientist should know about pathology: lessons from the - - PowerPoint PPT Presentation
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
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The Prostate
- 1. Description
- 2. Ink margins
- 3. Freeze for research
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90% 60% 5%
Frozen and FFPE samples are very heterogeneous
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Pathological assessment
- Gleason score
- pT-stage (extra-prostatic growth)
- Surgical margin
- Lymph node metastasis
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Gleason grading system
- 1966 - 2016: 50th anniversary
- Based on tumor growth patterns
- Accounts for tumor heterogeneity
- Modifications in 2005 and 2016
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Normal Gleason 3
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Gleason 5 Gleason 4
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Gleason score
Gleason score: 3 + 4 = 7 Gleason 4 Gleason 3
Accounts for heterogeneity: adding 2 most common patterns
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Gleason score 6 does not cause PCa death
3+3=6 3+4=7 4+3=7 >7 n = 1101
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Gleason score 3+4=7 on biopsy
“The 2 most common patterns” G3 55% G4 45% G3 99% G4 1% Gleason score 3+4=7
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Quantification of Grade 4 component
Sauter Eur Urol 2016
6 7 (4+3) 7 (3+4) 9-10 8
G4 % in GS 7 5% 6-10% 11-20% 7 (3+4) 21-30% 31-49% 50-60% 61-80% 7 (4+3) >80% 6 7 (4+3) 7 (3+4) 9-10 8
BCRFS after radical prostatectomy
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GG 3 GG 4 GG 5
κ κ
fused ill-formed glomeruloid cribriform
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Frequency Gleason grade 4 patterns
One pattern 22% Two patterns 47% Three patterns 26% Four patterns 5% Ill-defined 66% Fused 76% Glomeruloid 28% Cribriform 38%
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without cribriform with cribriform
Cribriform GS 7 at radical prostatectomy
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Cribriform GS 7 at biopsy
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Cribriform GS 7 at biopsy
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Cribriform GS 7 at biopsy: BCRFS
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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
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Biomarkers for risk stratification
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
Commercially available, standardized tests Validated in several studies Additive value to existing nomograms
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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
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“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
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Molecular biology of GS 3+4=7?
3+4=7 HE 3 3 3 4 cr 4 ill Growth patterns DNA/RNA Genomic black box
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Genomic instability in cribriform growth
Chua, Eur Urol 2017; Böttcher, Submitted
CR
- +
- +
+ + 6 3+4 4+3 8 9-10 GS
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GG4 cribriform: progressive genomic loss
GG3 Cribriform GG4
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Molecular background GG4 cribriform
CISH c-MYC in 20 prostate cancer specimens 500 cells counted (amplification if mean > 2.2)
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GG4 ill-defined: EMT/Cadherin switching
Kolijn, Oncotarget 2015
ill-defined GG4 N-Cadherin
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1674 2016 Microscopic evolution … ?
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Histopathologic delineation
? ? ? ?
Gleason grade 3
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GG 4 ill-formed
800 µm x z y Before After BABB clearing
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GG 4 ill-formed GG 3 glandular GG 4 cribriform
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Take home messages
- Gain basic knowledge of pathology
- Far more to say, than PA report only
- Contact your pathologist at early stage
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