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Saturday May 25, 2024 from 16:00 to 17:30

Room: Regency

> Poster POS-58 Cell state origins of endometriosis-associated malignancies

Svetlana Djirackor

Graduate Student
Epigenetics
Van Andel Institute

Abstract

Cell state origins of endometriosis-associated malignancies

Svetlana Djirackor1, Ian Beddows1, Emily Wolfrum2, Ben Johnson1, David Huntsman4,5, Michael Anglesio4,6, Celeste Leigh Pearce3, Hui Shen1.

1Department of Epigenetics, Van Andel Institute, Grand Rapids, MI, United States; 2Bioinformatics and Biostatistics Core, Van Andel Institute, Grand Rapids, MI, United States; 3Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, United States; 4Department of Obstetrics and Gynecology, University of British Columbia Vancouver, Vancouver, BC, Canada; 5Department of Pathology and Laboratory Medicine, University of British Columbia Vancouver, Vancouver, BC, Canada; 6Department of Molecular Oncology, British Columbia Cancer Research Institute, Vancouver, BC, Canada; 7British Columbia's Gynecological Cancer Research OVCARE) Program, University of British Columbia Vancouver, Vancouver, BC, Canada

Introduction: The endometrial epithelium (EE) is considered the cell of origin for endometriosis-associated clear cell (CCC) and endometrioid carcinoma (EC). We previously showed that transcription profiles of ovarian EC and CCC mirror those of the normal EE in proliferative and secretory phases of the menstrual cycle, respectively. We hypothesized that progenitor cells become “locked” in their cell states through epigenetic alterations, providing a means for mitotic inheritance of cell states through tumorigenesis. Here, we test this model by analyzing cancers arising from iatrogenic endometriosis (IE). As gestational EE from obstetric surgeries is considered hypersecretory, we propose that the predominant IE from obstetric surgeries would preferably give rise to CCC compared to non-obstetric surgeries (random state of EE). Methods: A literature search and meta-analysis was conducted on PubMed and Google Scholar using manually-curated search terms for reports of IE-associated carcinomas (IECs). Publications used in this analysis ranged from January 1980 to June 2023. Results: With a total of 113 IEC cases, we show that CCCs are enriched in obstetric vs non-obstetric surgeries (77% vs 40%). However, due to the sample imbalance between obstetric and non-obstetric cases (103 vs 10), we were not statistically powered to infer differences. To overcome this, we compared the incidence of CCC in obstetric surgeries to tumors from other extra-ovarian endometriosis (not surgically-induced) reported in the literature and confirmed a significant enrichment for CCC in IE from obstetric surgeries (77% vs 15%; p<0.05). Conclusions: To the best of our knowledge, this is the most comprehensive review of IECs to date, and, through our analyses, our data support our cell state model by showing enrichment of CCC in IECs from obstetric surgeries. This supports the idea that the originating cell state likely impacts CCC/EC distribution at the ovary.

Van Andel Institute . Van Andel Institute Graduate School.

Presentations by Svetlana Djirackor

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