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. 2013 Oct;22(10):1677-86.
doi: 10.1158/1055-9965.EPI-13-0391. Epub 2013 Jul 23.

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

Martin Köbel  1 , Steve E Kalloger, Sandra Lee, Máire 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 Benjamin, Simon A Gayther, Aleksandra Gentry-Maharaj, Usha Menon, C Blake Gilks, David G Huntsman, Susan J Ramus, Ellen L Goode; Ovarian Tumor Tissue Analysis consortium
Affiliations

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

Martin Köbel et al. Cancer Epidemiol Biomarkers Prev. 2013 Oct.

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.

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Conflict of interest statement

Disclosure of Potential Conflict of Interest: Usha Menon has a financial interest through UCL Business and Abcodia Ltd in the third party exploitation of clinical trials biobanks which have been developed through the research at UCL. The other authors declare no conflict of interest.

Figures

Figure 1
Figure 1. Histological type assignments in the testing set
Figure 2
Figure 2. Overall survivals of the testing set shown in univariate Kaplan-Meier analysis
Red is endometrioid carcinoma, Blue is high-grade serous carcinoma, yellow is clear cell carcinoma, green is mucinous carcinoma, light blue is low-grade serous carcinoma. P-values represent Wilcoxon test of survival difference across type assessments: A - original type, B - TB_COSPv2, C – agreement between original type and TB_COSPv2, D – agreement between 2 out of 3 methods of assessment (original type, TB_COSPv2 and WT1-assisted core review
See this image and copyright information in PMC

References

    1. Köbel M, Kalloger SE, Boyd N, McKinney S, Mehl E, Palmer C, et al. Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS Med. 2008;5:e232. - PMC - PubMed
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