in epithelial ovarian carcinoma Dr Kurosh Rahimi MD, MSc,FRCPC, - - PowerPoint PPT Presentation

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in epithelial ovarian carcinoma Dr Kurosh Rahimi MD, MSc,FRCPC, - - PowerPoint PPT Presentation

May 12, 2023 144 likes •301 views

Gynecologic Cancer InterGroup Imaging & Pathology Brainstorming Day October 2018 - Munich Integration of molecular markers in epithelial ovarian carcinoma Dr Kurosh Rahimi MD, MSc,FRCPC, CRCHUM-Montreal (Canada) COEUR program High grade

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Gynecologic Cancer InterGroup Imaging & Pathology Brainstorming Day October 2018 - Munich

Dr Kurosh Rahimi MD, MSc,FRCPC,

CRCHUM-Montreal (Canada)

Integration of molecular markers in epithelial ovarian carcinoma

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High grade serous 63% Low grade serous 15% Endometrioid 5% Clear Cell 13% Mucinous 4%

High grade serous Low grade serous Endometrioid Clear Cell Mucinous LGSC

J Natl Cancer Inst. April 28, 2018. doi:10.1093/jnci/djy072- Peres et al. (American cohort)

N=16057 EC Overall Survival in EOC

COEUR program

HGSC CCC MC

EOC 5 distinct histotypes

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SLIDE 3
  • To improve the clinical management of ovarian

cancer patients, the COEUR program proposed to:

➢ Develop an unique platform

  • f

Canadian banked biospecimens annotated with clinical data. ➢ Validate biomarkers that can be used in the stratification of

  • varian cancer patients.

➢ Integrate molecular studies to build a unique nomogram of molecular signatures.

COEUR program

a pan-Canadian biomarker validation platform

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COEUR program

a pan-Canadian biomarker validation platform

Pathology Gynecologic oncology Medical oncology Fundamental scientist

5 provinces- 2 languages 12 biobanks- 16 hospitals

  • RRC- CHUM (Montreal, QC)
  • RRC-CHU Quebec (Quebec, QC)
  • RRC-CHU Sherbrooke (Sherbrooke, QC)
  • RRC-McGill University–LDI (Montreal, QC)
  • Ontario Health Reasearch Institute (Ottawa, ON)
  • Ontario Tumor Bank (Toronto, ON)
  • UHN Biobank (Toronto, ON)
  • Sunnybrooke biobank (Toronto, ON)
  • Biobank of Cancer Breast Cancer Fundation

(Calgary/Edmonton, AB)

  • Manitoba Ovarian Biobank Program (Winnipeg, MB)
  • OvCare (Vancouver, BC)
  • Tumor Tissue Repository (Victoria, BC)
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Biobanking process

Informed consent PATIENTS Lab/pathology blood ascites Tumor tissue

Frozen tissue FFPE Plasma/serum

processing

Storage

DNA/RNA extraction

microarray cut slides/IHC

INVESTIGATORS REB

genomics IHC/IF proteomics

Database Biospecimen repository

Quality control

Inventory Lab report Research data Clinical data Pathology report

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SLIDE 6

biobanking

Frozen Tissue FFPE Blood (normal tissue)

IHC/IF/FISH proteomics DNA-RNA Proteomics (expression, structure) cut slides Genotyping sequencing epigenomics

Biospecimens Processing/QA Derivates Analysis

Tumor Tissue Ascites Cell separation serum plasma Cell separation Ascites fluid

DNA-RNA Genotyping sequencing epigenomics

Translational use Biomarkers (diagnostic

Pronostic Molecular classification Therapeutic target)

Therapeutic Targets Drugs evaluation

New methods

  • f diagnostic

microarray DNA-RNA Primary culture Primary culture

Cell culture

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SLIDE 7

Whole slide FFPE H&E Pathologist 1 Pathologist 2 (CosPv3 panel)

Final histotyping

P53 WT1 P16 ER/PR ARID1A TFF3 Vim Napsin

Histotyping: 2-step pathology review

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BDL HGSC EC LGSC CCC MC HGSC 1 1135 13 28 9 2 EC 1 43 268 2 LGSC 8 19 66 CCC 1 4 4 248 MC 10 6 9 84 Original registry file

The most common errors are found in Endometrioid and Low Grade Serous Carcinoma

Original registry file Revised histotypying

Histotyping: 2-step pathology review

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SLIDE 12

Re-Histotyping: Effect on outcome

Low grade serous carcinoma and mucinous have a worse prognostic than usually reported and need a closer follow-up of patients and personalized medecine Advanced stages diseases

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P16 in Low grade serous EOC

P=0.068 P=0.032

CDK4/6 should be considered as a therapeutic target In Low Grade Serous carcinoma

Before histotyping After histotyping

p16

CDK4/6

Re-Histotyping: Effect on biomarker evaluation

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Non carrier 75% BRCA1 14% BRCA2 7% Double BRCA1/2 1% VUS 3%

BRCA INCIDENCE in HGSC

Non carrier BRCA1 BRCA2 Double BRCA1/2

WT BRCA BRCA- VUS HGSC 750 110 (15%) 17 LGSC 62 3 (5%) EC 92 1 (1%) 1 CCC 54 1 (1%)

BRCA germline mutation is largely restricted to High Grade Serous cases BRCA carriers, and particularly BRCA2, carriers have a better survival than WT

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Biobanking Molecular pathology platform

Fundamental research

COEUR team

Lise Portelance Manon deLadurantaye Jennifer Dupont Kim Leclerc-Deslaulniers Anne-Marie Mes-Masson Diane Provencher Kurosh Rahimi

Principal investigators

Liliane Meunier Veronique Barres Christine Caron Euridice Carmona Hubert Fleury Laudine communal Kossay Zaoui

  • Anne-Marie Mes-Masson, Diane Provencher, David

Huntsman (directors)

  • Kurosh Rahimi, Martin Kobel, John Bartlett, (Pathologits)
  • Patricia Tonin, Barbara Vanderhyden, Brad Nelson, Anna

Tinker, Stéphnie Scott, Stéphanie Lheureux (S. C.)

  • Walter Gotlieb, Dimcho Bachravov, Mark Nachtigal, Alain

Piché, Marcus Bernardini, Peter Watson (biobanks)

  • Cécile Le Page (Coodinator)

ACKNOWLEDGMENTS