Dataset Information

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. 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.

SUBMITTER: Kobel M

PROVIDER: S-EPMC3955399 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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

Köbel Martin M Kalloger Steve E SE Lee Sandra S Duggan Máire A MA Kelemen Linda E LE Prentice Leah L Kalli Kimberly R KR Fridley Brooke L BL Visscher Daniel W DW Keeney Gary L GL Vierkant Robert A RA Cunningham Julie M JM Chow Christine C Ness Roberta B RB Moysich Kirsten K Edwards Robert R Modugno Francesmary F Bunker Clareann C Wozniak Eva L EL Benjamin Elizabeth E Gayther Simon A SA Gentry-Maharaj Aleksandra A Menon Usha U Gilks C Blake CB Huntsman David G DG Ramus Susan J SJ Goode Ellen L EL

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20130723 10

<h4>Background</h4>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.<h4>Methods</h4>Tissue microarrays (TMA) and clinical data were available for 524 pathologically confirmed ovarian carcinomas. Centralized IHC was conducted for ARI ...[more]

PMID: 23880734

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Project description:Tumor budding in colorectal carcinoma has been associated with poor outcome in multiple studies, but the absence of an established histologic cutoff for "high" tumor budding, heterogeneity in study populations, and varying methods for assessing tumor budding have hindered widespread incorporation of this parameter in clinical reports. We used an established scoring system in a population-based cohort to determine a histologic cutoff for "high" tumor budding and confirm its prognostic significance. We retrieved hematoxylin and eosin-stained sections from 553 incident colorectal carcinoma cases. Each case was previously characterized for select molecular alterations and survival data. Interobserver agreement was assessed between 2 gastrointestinal pathologists and a group of 4 general surgical pathologists. High budding (≥ 10 tumor buds in a ×20 objective field) was present in 32% of cases, low budding in 46%, and no budding in 22%. High tumor budding was associated with advanced pathologic stage (P < 0.001), microsatellite stability (P = 0.005), KRAS mutation (P = 0.010), and on multivariate analysis with a > 2 times risk of cancer-specific death (hazard ratio = 2.57 [1.27, 5.19]). After multivariate adjustment, by penalized smoothing splines, we found increasing tumor bud counts from 5 upward to be associated with an increasingly shortened cancer-specific survival. By this method, a tumor bud count of 10 corresponded to approximately 2.5 times risk of cancer-specific death. The interobserver agreement was good with weighted κ of 0.70 for 2 gastrointestinal pathologists over 121 random cases and 0.72 between all 6 pathologists for 20 random cases. Using an established method to assess budding on routine histologic stains, we have shown that a cutoff of 10 for high tumor budding is independently associated with a significantly worse prognosis. The reproducibility data provide support for the routine widespread implementation of tumor budding in clinical reports.

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Dataset Information

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

Publications

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

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