Characteristics and outcome of the COEUR Canadian validation cohort for ovarian cancer biomarkers

BMC Cancer

Liliane Meunier¹  David G. Huntsman²  Peter H. Watson³  Walter H. Gotlieb⁴  Anne-Marie Mes-Masson⁵  Lise Portelance⁵  Cécile Le Page⁵  Kurosh Rahimi⁵  Brad H. Nelson⁵  Monique Bernard⁵  Alain Piché⁶  John M. S. Bartlett⁷  Martin Köbel⁸  Mark W. Nachtigal⁹  Diane M. Provencher⁹  Jessica N. McAlpine⁹  Patricia N. Tonin^1,10  Dimcho Bachvarov^1,11  Blake Gilks^1,12  Barbara Vanderhyden^1,13  Marcus Q. Bernardini^1,13 

[1] Cancer Research Program, The Research Institute of the McGill University Health Centre;Cancer Therapeutics Program, Ottawa Hospital Research Institute;Centre de Recherche du CHUS. Département de Microbiologie et Infectiologie, Faculté de Médecine, Université de Sherbrooke;Centre de recherche du CHU de Quebec;Centre de recherche du Centre hospitalier de l’Université de Montréal (CRCHUM) and Institut du cancer de Montréal;Department of Biochemistry & Medical Genetics, University of Manitoba;Department of Obstetrics and Gynaecology, University of Toronto;Department of Pathology and Laboratory of Medicine, University of Calgary;Department of Pathology, Vancouver General Hospital and University of British Columbia;Departments of Medicine and Human Genetics, McGill University;Diagnostic Development and Ontario Tumour Bank, Ontario Institute for Cancer Research;Laboratory of Gynecologic Oncology, Lady Davis Research Institute, Jewish General Hospital;Tumour Tissue Repository, Trev and Joyce Deeley Research Centre, BC Cancer Agency;

关键词: Epithelial ovarian cancer;    Histotype;    Biomarker;    BRCA;    Survival;    Treatment response;   

DOI  :  10.1186/s12885-018-4242-8

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown