Dedifferentiated and undifferentiated ovarian carcinoma: an aggressive and molecularly distinct ovarian tumor characterized by frequent SWI/SNF complex inactivation
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 multiinstituti...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
January 2024
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| In: |
Modern pathology
Year: 2024, Volume: 37, Issue: 1, Pages: 1-12 |
| ISSN: | 1530-0285 |
| DOI: | 10.1016/j.modpat.2023.100374 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.modpat.2023.100374 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S089339522300279X?via%3Dihub 
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| Author Notes: | Basile Tessier-Cloutier, Felix K.F. Kommoss, David L. Kolin, Kristyna Nemejcova, Dupreez Smith, Jennifer Pors, Colin J.R. Stewart, W. Glenn Mccluggage, William D. Foulkes, Andreas von Deimling, Martin Kobel, Cheng-Han Lee |
| Summary: | 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 multiinstitutional 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 IIeIV 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 |
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| Item Description: | Gesehen am 02.08.2024 Online veröffentlicht: 03. November 2023 |
| Physical Description: | Online Resource |
| ISSN: | 1530-0285 |
| DOI: | 10.1016/j.modpat.2023.100374 |