Biomarker-Based Ovarian Carcinoma Typing: A Histologic Investigation in the Ovarian Tumor Tissue Analysis Consortium
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Published:2013-10-01
Issue:10
Volume:22
Page:1677-1686
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ISSN:1055-9965
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Container-title:Cancer Epidemiology, Biomarkers & Prevention
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language:en
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Short-container-title:
Author:
Köbel Martin1, Kalloger Steve E.1, Lee Sandra1, Duggan Máire A.1, Kelemen Linda E.1, Prentice Leah1, Kalli Kimberly R.1, Fridley Brooke L.1, Visscher Daniel W.1, Keeney Gary L.1, Vierkant Robert A.1, Cunningham Julie M.1, Chow Christine1, Ness Roberta B.1, Moysich Kirsten1, Edwards Robert111, Modugno Francesmary111, Bunker Clareann1, Wozniak Eva L.1, Benjamin Elizabeth1, Gayther Simon A.1, Gentry-Maharaj Aleksandra1, Menon Usha1, Gilks C. Blake1, Huntsman David G.1, Ramus Susan J.1, Goode Ellen L.1
Affiliation:
1. Authors' Affiliations: 1Department of Pathology and Laboratory Medicine; 2Department of Population Health Research, Alberta Health Services-Cancer Care and Department of Medical Genetics, University of Calgary, Calgary, Alberta; 3Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada; 4Department of Medical Oncology; 5Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology; 6Division of Biomedical Statistics and Informatics, Department of Health Science Research; 7Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology; 8Division of Epidemiology, Department of Health Science Research, Mayo Clinic, Rochester, Minnesota; 9Biostatistics and Informatics Shared Resource, University of Kansas Medical Center, Kansas City, Kansas; 10University of Texas School of Public Health, Houston, Texas; 11Roswell Park Cancer Institute, Buffalo, New York, New York; 12Women's Cancer Research C
Abstract
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.
Impact: Biomarker-based classification of ovarian carcinomas is feasible, improves comparability of results across research studies, and can reclassify cases which lack reliable original pathology. Cancer Epidemiol Biomarkers Prev; 22(10); 1677–86. ©2013 AACR.
Publisher
American Association for Cancer Research (AACR)
Cited by
72 articles.
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