Biomarker-based ovarian carcinoma typing: A histologic investigation in the ovarian tumor tissue analysis consortium

Martin Köbel, Steve E. Kalloger, Sandra Lee, Maire A. Duggan, Linda E. Kelemen, Leah Prentice, Kimberly R. Kalli, Brooke L. Fridley, Daniel W. Visscher, Gary L. Keeney, Robert A. Vierkant, Julie M. Cunningham, Christine Chow, Roberta B. Ness, Kirsten Moysich, Robert Edwards, Francesmary Modugno, Clareann Bunker, Eva L. Wozniak, Elizabeth BenjaminSimon A. Gayther, Aleksandra Gentry-Maharaj, Usha Menon, C. Blake Gilks, David G. Huntsman, Susan J. Ramus, Ellen L. Goode

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1677-1686
Number of pages10
JournalCancer Epidemiology Biomarkers and Prevention
Issue number10
StatePublished - Oct 2013

ASJC Scopus subject areas

  • General Medicine


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