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Characteristics and outcome of the COEUR Canadian validation cohort for ovarian cancer biomarkers Le Page, Cécile; Rahimi, Kurosh; Köbel, Martin; Tonin, Patricia N; Meunier, Liliane; Portelance, Lise; Bernard, Monique; Nelson, Brad H; Bernardini, Marcus Q; Bartlett, John M S; et al.

Abstract

Background: Ovarian carcinoma is the most lethal gynecological malignancy due to early dissemination and acquired resistance to platinum-based chemotherapy. Reliable markers that are independent and complementary to clinical parameters are needed to improve the management of patients with this disease. The Canadian Ovarian Experimental Unified Resource (COEUR) provides researchers with biological material and associated clinical data to conduct biomarker validation studies. Using standards defined by the Canadian Tissue Repository Network (CTRNet), we have previously demonstrated the quality of the biological material from this resource. Here we describe the clinical characteristics of the COEUR cohort. Methods: With support from 12 Canadian ovarian cancer biobanks in Canada, we created a central retrospective cohort comprised of more than 2000 patient tissue samples with associated clinical data, including 1246 high-grade serous, 102 low-grade serous, 295 endometrioid, 259 clear cell and 89 mucinous carcinoma histotypes. A two-step reclassification process was applied to assure contemporary histological classification (histotyping). For each histotypes individually, we evaluated the association between the known clinico-pathological parameters (stage, cytoreduction, chemotherapy treatment, BRCA1 and BRCA2 mutation) and patient outcome by using Kaplan-Meier and Cox proportional hazard regression analyses. Results: The median follow-up time of the cohort was 45 months and the 5-year survival rate for patients with high-grade serous carcinomas was 34%, in contrast to endometrioid carcinomas with 80% at 5 years. Survival profiles differed by histotype when stratified by stage or cytoreduction. Women with mucinous or clear cell carcinomas at advanced stage or with non-optimally debulked disease had the worst outcomes. In high-grade serous carcinoma, we observed significant association with longer survival in women harboring BRCA1 or BRCA2 mutation as compared to patients without detectable mutation. Conclusions: Our results show the expected survival rates, as compared with current literature, in each histotype suggesting that the cohort is an unbiased representation of the five major histotypes. COEUR, a one stop comprehensive biorepository, has collected mature outcome data and relevant clinical data in a comprehensive manner allowing stratified analysis.

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Title
Characteristics and outcome of the COEUR Canadian validation cohort for ovarian cancer biomarkers
Creator
Le Page, Cécile; Rahimi, Kurosh; Köbel, Martin; Tonin, Patricia N; Meunier, Liliane; Portelance, Lise; Bernard, Monique; Nelson, Brad H; Bernardini, Marcus Q; Bartlett, John M S; Bachvarov, Dimcho; Gotlieb, Walter H; Gilks, Blake; McAlpine, Jessica N; Nachtigal, Mark W; Piché, Alain; Watson, Peter H; Vanderhyden, Barbara; Huntsman, David G; Provencher, Diane M; Mes-Masson, Anne-Marie
Publisher
BioMed Central
Date Issued
2018-03-27
Description
Background: Ovarian carcinoma is the most lethal gynecological malignancy due to early dissemination and acquired resistance to platinum-based chemotherapy. Reliable markers that are independent and complementary to clinical parameters are needed to improve the management of patients with this disease. The Canadian Ovarian Experimental Unified Resource (COEUR) provides researchers with biological material and associated clinical data to conduct biomarker validation studies. Using standards defined by the Canadian Tissue Repository Network (CTRNet), we have previously demonstrated the quality of the biological material from this resource. Here we describe the clinical characteristics of the COEUR cohort. Methods: With support from 12 Canadian ovarian cancer biobanks in Canada, we created a central retrospective cohort comprised of more than 2000 patient tissue samples with associated clinical data, including 1246 high-grade serous, 102 low-grade serous, 295 endometrioid, 259 clear cell and 89 mucinous carcinoma histotypes. A two-step reclassification process was applied to assure contemporary histological classification (histotyping). For each histotypes individually, we evaluated the association between the known clinico-pathological parameters (stage, cytoreduction, chemotherapy treatment, BRCA1 and BRCA2 mutation) and patient outcome by using Kaplan-Meier and Cox proportional hazard regression analyses. Results: The median follow-up time of the cohort was 45 months and the 5-year survival rate for patients with high-grade serous carcinomas was 34%, in contrast to endometrioid carcinomas with 80% at 5 years. Survival profiles differed by histotype when stratified by stage or cytoreduction. Women with mucinous or clear cell carcinomas at advanced stage or with non-optimally debulked disease had the worst outcomes. In high-grade serous carcinoma, we observed significant association with longer survival in women harboring BRCA1 or BRCA2 mutation as compared to patients without detectable mutation. Conclusions: Our results show the expected survival rates, as compared with current literature, in each histotype suggesting that the cohort is an unbiased representation of the five major histotypes. COEUR, a one stop comprehensive biorepository, has collected mature outcome data and relevant clinical data in a comprehensive manner allowing stratified analysis.
Subject
Epithelial ovarian cancer; Histotype; Biomarker; BRCA; Survival; Treatment response
Genre
Article
Type
Text
Language
eng
Date Available
2018-03-28
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0364561
URI
http://hdl.handle.net/2429/64985
Affiliation
Medicine, Faculty of; Non UBC; Obstetrics and Gynaecology, Department of; Pathology and Laboratory Medicine, Department of
Citation
BMC Cancer. 2018 Mar 27;18(1):347
Publisher DOI
10.1186/s12885-018-4242-8
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
The Author(s).
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)