title: An Immunohistochemical Algorithm for Ovarian Carcinoma Typing.
abstract: There are 5 major histotypes of ovarian carcinomas. Diagnostic typing criteria have evolved over time, and past cohorts may be misclassified by current standards. Our objective was to reclassify the recently assembled Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type cohorts using immunohistochemical (IHC) biomarkers and to develop an IHC algorithm for ovarian carcinoma histotyping. A total of 1626 ovarian carcinoma samples from the Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type were subjected to a reclassification by comparing the original with the predicted histotype. Histotype prediction was derived from a nominal logistic regression modeling using a previously reclassified cohort (N=784) with the binary input of 8 IHC markers. Cases with discordant original or predicted histotypes were subjected to arbitration. After reclassification, 1762 cases from all cohorts were subjected to prediction models (χ Automatic Interaction Detection, recursive partitioning, and nominal logistic regression) with a variable IHC marker input. The histologic type was confirmed in 1521/1626 (93.5%) cases of the Canadian Ovarian Experimental Unified Resource and the Alberta Ovarian Tumor Type cohorts. The highest misclassification occurred in the endometrioid type, where most of the changes involved reclassification from endometrioid to high-grade serous carcinoma, which was additionally supported by mutational data and outcome. Using the reclassified histotype as the endpoint, a 4-marker prediction model correctly classified 88%, a 6-marker 91%, and an 8-marker 93% of the 1762 cases. This study provides statistically validated, inexpensive IHC algorithms, which have versatile applications in research, clinical practice, and clinical trials.
authors.affiliation: Calgary Laboratory Services/Alberta Health Services (M.K., P.F.R., C.N., S.L.), Department of Pathology and Laboratory Medicine, Foothill Medical Center, University of Calgary, Calgary Department of Laboratory Medicine and Pathology (X.L., C.A.E., C.-H.L.), University of Alberta, Edmonton, AB Centre de recherche du (K.R., C.L.P., L.M., M.d.L., D.P., A.-M.M.M.), Centre hospitalier de l'Université de Montréal (CRCHUM) Departments of Pathology (K.R.) Obstetric-Gynecology (D.P.) Medicine (A.-M.M.M.), Université de Montréal Institut du cancer de Montréal (C.L.P., L.M., M.d.L., D.P., A.-M.M.M.), Montreal, QC Department of Pathology (S.L., D.H., C.B.G.), University of British Columbia, Vancouver, BC Department of Cellular and Molecular Medicine (B.V.), University of Ottawa, ON, Canada Department of Pathology (P.F.R.), Catholic University of Health and Allied Sciences-Bugando, Mwanza, Tanzania Department of Health Sciences Research (E.L.G.), Mayo Clinic, Rochester, Minnesota Department of Preventive Medicine (S.J.R.), Keck School of Medicine, USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California Department of Pathology and Cytology (J.W.C.), Institution for Oncology-Pathology, Karolinska University Hospital, Stockholm, Sweden Department of Public Health Sciences (L.E.K.), College of Medicine, Medical University of South Carolina Hollings Cancer Center (L.E.K.), Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
authors.forename: Kurosh
authors.initials: K
authors.lastname: Rahimi
authors.forename: Peter F
authors.initials: PF
authors.lastname: Rambau
authors.forename: Christopher
authors.initials: C
authors.lastname: Naugler
authors.forename: Cécile
authors.initials: C
authors.lastname: Le Page
authors.forename: Liliane
authors.initials: L
authors.lastname: Meunier
authors.forename: Manon
authors.initials: M
authors.lastname: de Ladurantaye
authors.forename: Sandra
authors.initials: S
authors.lastname: Lee
authors.forename: Samuel
authors.initials: S
authors.lastname: Leung
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Ramus
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Carlson
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.forename: Carol A
authors.initials: CA
authors.lastname: Ewanowich
authors.forename: Linda E
authors.initials: LE
authors.lastname: Kelemen
authors.forename: Barbara
authors.initials: B
authors.lastname: Vanderhyden
authors.forename: Diane
authors.initials: D
authors.lastname: Provencher
authors.forename: David
authors.initials: D
authors.lastname: Huntsman
authors.forename: Cheng-Han
authors.initials: CH
authors.lastname: Lee
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mes Masson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002170:Canada; D002277:Carcinoma / Q000145:classification* / Q000473:pathology; D018269:Carcinoma, Endometrioid / Q000145:classification* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000145:classification* / Q000473:pathology; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor