title: Biomarker-based ovarian carcinoma typing: a histologic investigation in the ovarian tumor tissue analysis consortium.
abstract: BACKGROUND
  Ovarian carcinoma is composed of five major histologic types, which associate with outcome and predict therapeutic response. Our aim was to evaluate histologic type assessments across the centers participating in the Ovarian Tumor Tissue Analysis (OTTA) consortium using an immunohistochemical (IHC) prediction model.
  
  
  METHODS
  Tissue microarrays (TMA) and clinical data were available for 524 pathologically confirmed ovarian carcinomas. Centralized IHC was conducted for ARID1A, CDKN2A, DKK1, HNF1B, MDM2, PGR, TP53, TFF3, VIM, and WT1, and three histologic type assessments were compared: the original pathologic type, an IHC-based calculated type (termed TB_COSPv2), and a WT1-assisted TMA core review.
  
  
  RESULTS
  The concordance between TB_COSPv2 type and original type was 73%. Applying WT1-assisted core review, the remaining 27% discordant cases subdivided into unclassifiable (6%), TB_COSPv2 error (6%), and original type error (15%). The largest discordant subgroup was classified as endometrioid carcinoma by original type and as high-grade serous carcinoma (HGSC) by TB_COSPv2. When TB_COSPv2 classification was used, the difference in overall survival of endometrioid carcinoma compared with HGSC became significant [RR 0.60; 95% confidence interval (CI), 0.37-0.93; P = 0.021], consistent with previous reports. In addition, 71 cases with unclear original type could be histologically classified by TB_COSPv2.
  
  
  CONCLUSIONS
  Research cohorts, particularly those across different centers within consortia, show significant variability in original histologic type diagnosis. Our IHC-based reclassification produced more homogeneous types with respect to outcome than original type.
  
  
  CONCLUSIONS
  Biomarker-based classification of ovarian carcinomas is feasible, improves comparability of results across research studies, and can reclassify cases which lack reliable original pathology.
authors.affiliation: Authors' Affiliations: Department of Pathology and Laboratory Medicine; Department of Population Health Research, Alberta Health Services-Cancer Care and Department of Medical Genetics, University of Calgary, Calgary, Alberta; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; Department of Medical Oncology; Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology; Division of Biomedical Statistics and Informatics, Department of Health Science Research; Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology; Division of Epidemiology, Department of Health Science Research, Mayo Clinic, Rochester, Minnesota; Biostatistics and Informatics Shared Resource, University of Kansas Medical Center, Kansas City, Kansas; University of Texas School of Public Health, Houston, Texas; Roswell Park Cancer Institute, Buffalo, New York, New York; Women's Cancer Research Center, Magee-Womens Research Institute, University of Pittsburgh Cancer Institute; Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania; Gynaecological Cancer Research Centre, Women's Cancer, UCL EGA Institute for Women's Health; Department of Pathology, Cancer Institute, UCL, London, United Kingdom; and Department of Preventive Medicine, Keck School of Medicine, USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California.
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
authors.forename: Steve E
authors.initials: SE
authors.lastname: Kalloger
authors.forename: Sandra
authors.initials: S
authors.lastname: Lee
authors.forename: Máire A
authors.initials: MA
authors.lastname: Duggan
authors.forename: Linda E
authors.initials: LE
authors.lastname: Kelemen
authors.forename: Leah
authors.initials: L
authors.lastname: Prentice
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Kalli
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Visscher
authors.forename: Gary L
authors.initials: GL
authors.lastname: Keeney
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Julie M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: Christine
authors.initials: C
authors.lastname: Chow
authors.forename: Roberta B
authors.initials: RB
authors.lastname: Ness
authors.forename: Kirsten
authors.initials: K
authors.lastname: Moysich
authors.forename: Robert
authors.initials: R
authors.lastname: Edwards
authors.forename: Francesmary
authors.initials: F
authors.lastname: Modugno
authors.forename: Clareann
authors.initials: C
authors.lastname: Bunker
authors.forename: Eva L
authors.initials: EL
authors.lastname: Wozniak
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Benjamin
authors.forename: Simon A
authors.initials: SA
authors.lastname: Gayther
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: David G
authors.initials: DG
authors.lastname: Huntsman
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Ramus
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D000077216:Carcinoma, Ovarian Epithelial; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry* / Q000145:classification* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000145:classification* / Q000473:pathology; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor