학술논문
Dedifferentiated and Undifferentiated Ovarian Carcinoma: An Aggressive and Molecularly Distinct Ovarian Tumor Characterized by Frequent SWI/SNF Complex Inactivation.
Document Type
Academic Journal
Author
Tessier-Cloutier B; Department of Pathology and Laboratory Medicine, McGill University Health Centre, Montreal, Quebec, Canada.; Kommoss FKF; Institute of Pathology, University of Heidelberg, Heidelberg, Germany.; Kolin DL; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.; Němejcová K; Department of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.; Smith D; Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada.; Pors J; Department of Pathology and Laboratory Medicine, BC Cancer, Vancouver, British Columbia, Canada.; Stewart CJR; Department of Pathology, King Edward Memorial Hospital, Perth, Australia.; McCluggage WG; Department of Pathology, Belfast Health and Social Care Trust, Belfast, United Kingdom.; Foulkes WD; Departments of Human Genetics, McGill University, Montreal, Quebec, Canada.; von Deimling A; Department of Neuropathology, University Hospital Heidelberg, Heidelberg, Germany; CCU Neuropathology, German Cancer Center (DKFZ), Heidelberg, Germany.; Köbel M; Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.; Lee CH; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, Canada. Electronic address: chlee2@ualberta.ca.
Source
Publisher: Elsevier Inc Country of Publication: United States NLM ID: 8806605 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-0285 (Electronic) Linking ISSN: 08933952 NLM ISO Abbreviation: Mod Pathol Subsets: MEDLINE
Subject
Language
English
Abstract
Dedifferentiated and undifferentiated ovarian carcinomas (DDOC/UDOC) are rare neoplasms defined by the presence of an undifferentiated carcinoma. In this study, we detailed the clinical, pathological, immunohistochemical, and molecular features of a series of DDOC/UDOC. We collected a multi-institutional cohort of 23 DDOC/UDOC and performed immunohistochemistry for core switch/sucrose nonfermentable (SWI/SNF) complex proteins (ARID1A, ARID1B, SMARCA4, and SMARCB1), mismatch repair (MMR) proteins, and p53. Array-based genome-wide DNA methylation and copy number variation analyses were performed on a subset of cases with comparison made to a previously reported cohort of undifferentiated endometrial carcinoma (UDEC), small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), and tubo-ovarian high-grade serous carcinoma (HGSC). The age of all 23 patients with DDOC/UDOC ranged between 22 and 71 years (with an average age of 50 years), and a majority of them presented with extraovarian disease (16/23). Clinical follow-up was available for 19 patients. Except for 2 patients, the remaining 17 patients died from disease, with rapid disease progression resulting in mortality within a year in stage II-IV settings (median disease-specific survival of 3 months). Eighteen of 22 cases with interpretable immunohistochemistry results showed loss of expression of core SWI/SNF protein(s) that are expected to result in SWI/SNF complex inactivation as 10 exhibited coloss of ARID1A and ARID1B, 7 loss of SMARCA4, and 1 loss of SMARCB1. Six of 23 cases were MMR-deficient. Two of 20 cases exhibited mutation-type p53 immunoreactivity. Methylation profiles showed coclustering of DDOC/UDOC with UDEC, which collectively were distinct from SCCOHT and HGSC. However, DDOC/UDOC showed an intermediate degree of copy number variation, which was slightly greater, compared with SCCOHT but much less compared with HGSC. Overall, DDOC/UDOC, like its endometrial counterpart, is highly aggressive and is characterized by frequent inactivation of core SWI/SNF complex proteins and MMR deficiency. Its molecular profile overlaps with UDEC while being distinct from SCCOHT and HGSC.
(Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)
(Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)