title: Morphologic and Molecular Characteristics of Mixed Epithelial Ovarian Cancers.
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.
authors.affiliation: *Department of Molecular Oncology §Cancer Control Research, BC Cancer Agency Cancer Research Centre †Department of Pathology and Laboratory Medicine ‡Genetic Pathology Evaluation Centre, Anatomical Pathology at the Vancouver General Hospital ‡‡Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, BC, Canada ∥Department of Internal Medicine, University of New Mexico, Albuquerque, NM §§Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, AB ¶The Leeds Teaching Hospitals NHS Trust, Leeds #Barts Health NHS Trust, London, United Kingdom **Institut für Pathologie, Referenzzentrum für Gynäkopathologie, Mannheim ††Gynecologic Oncology Center, Kiel ∥∥Department of Gynecology and Obstetrics, Tuebingen University Women's Hospital, Tuebingen, Germany.
authors.forename: Robertson
authors.initials: R
authors.lastname: Mackenzie
authors.forename: Aline
authors.initials: A
authors.lastname: Talhouk
authors.forename: Sima
authors.initials: S
authors.lastname: Eshragh
authors.forename: Sherman
authors.initials: S
authors.lastname: Lau
authors.forename: Daphne
authors.initials: D
authors.lastname: Cheung
authors.forename: Christine
authors.initials: C
authors.lastname: Chow
authors.forename: Nhu
authors.initials: N
authors.lastname: Le
authors.forename: Linda S
authors.initials: LS
authors.lastname: Cook
authors.forename: Nafisa
authors.initials: N
authors.lastname: Wilkinson
authors.forename: Jacqueline
authors.initials: J
authors.lastname: McDermott
authors.forename: Naveena
authors.initials: N
authors.lastname: Singh
authors.forename: Friedrich
authors.initials: F
authors.lastname: Kommoss
authors.forename: Jacobus
authors.initials: J
authors.lastname: Pfisterer
authors.forename: David G
authors.initials: DG
authors.lastname: Huntsman
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
authors.forename: Stefan
authors.initials: S
authors.lastname: Kommoss
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: Michael S
authors.initials: MS
authors.lastname: Anglesio
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000416:Alberta; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001706:Biopsy; D001955:British Columbia; D018269:Carcinoma, Endometrioid / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000077216:Carcinoma, Ovarian Epithelial; D004252:DNA Mutational Analysis; D005060:Europe; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D018193:Neoplasms, Complex and Mixed / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D011237:Predictive Value of Tests
chemical_list: D014408:Biomarkers, Tumor