1. Morphologic and Molecular Characteristics of Mixed Epithelial Ovarian Cancers.
- Author
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Mackenzie R, Talhouk A, Eshragh S, Lau S, Cheung D, Chow C, Le N, Cook LS, Wilkinson N, McDermott J, Singh N, Kommoss F, Pfisterer J, Huntsman DG, Köbel M, Kommoss S, Gilks CB, and Anglesio MS
- Subjects
- Adenocarcinoma, Mucinous chemistry, Adenocarcinoma, Mucinous genetics, Adenocarcinoma, Mucinous pathology, Alberta, Biopsy, British Columbia, Carcinoma, Endometrioid chemistry, Carcinoma, Endometrioid genetics, Carcinoma, Endometrioid pathology, Carcinoma, Ovarian Epithelial, DNA Mutational Analysis, Europe, Female, Gene Expression Profiling, Genetic Predisposition to Disease, Humans, Immunohistochemistry, Neoplasms, Complex and Mixed chemistry, Neoplasms, Complex and Mixed genetics, Neoplasms, Complex and Mixed pathology, Neoplasms, Glandular and Epithelial chemistry, Neoplasms, Glandular and Epithelial genetics, Neoplasms, Glandular and Epithelial pathology, Ovarian Neoplasms chemistry, Ovarian Neoplasms genetics, Ovarian Neoplasms pathology, Phenotype, Predictive Value of Tests, Adenocarcinoma, Mucinous diagnosis, Biomarkers, Tumor analysis, Biomarkers, Tumor genetics, Carcinoma, Endometrioid diagnosis, Neoplasms, Complex and Mixed diagnosis, Neoplasms, Glandular and Epithelial diagnosis, Ovarian Neoplasms diagnosis
- Abstract
Epithelial ovarian cancer (EOC) consists of 5 major histotypes: high-grade serous carcinoma (HGSC), endometrioid carcinoma (EC), clear cell carcinoma (CCC), mucinous carcinoma (MC), and low-grade serous carcinoma (LGSC). Each can have a broad spectrum of morphologic appearances, and 1 histotype can closely mimic histopathologic features more typical of another. Historically, there has been a relatively high frequency of mixed, defined by 2 or more distinct histotypes present on the basis of routine histopathologic assessment, histotype carcinoma diagnoses (3% to 11%); however, recent immunohistochemical (IHC) studies identifying histotype-specific markers and allowing more refined histotype diagnoses suggest a much lower incidence. We reviewed hematoxylin and eosin-stained slides from 871 cases of EOC and found the frequency of mixed carcinomas to be 1.7% when modern diagnostic criteria are applied. Through international collaboration, we established a cohort totaling 22 mixed EOCs, consisting of 9 EC/CCC, 4 EC/LGSC, 3 HGSC/CCC, 2 CCC/MC, and 4 other combinations. We interrogated the molecular differences between the different components of each case using IHC, gene expression, and hotspot sequencing analyses. IHC data alone suggested that 9 of the 22 cases were not mixed tumors, as they presented a uniform immuno-phenotype throughout, and these cases most probably represent morphologic mimicry and variation within tumors of a single histotype. Synthesis of molecular data further reduces the incidence of mixed carcinomas. On the basis of these results, true mixed carcinomas with both morphologic and molecular support for the presence of >1 histotype within a given tumor represent <1% of EOCs.
- Published
- 2015
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