367 Alterations in the immune microenvironment of endometriosis and endometriosis associated ovarian carcinoma: a longitudinal cohort study

Introduction/Background Chronic inflammation in ovarian endometriosis may be pivotal in the development of endometriosis-associated ovarian carcinoma (EAOC). However, immune factors involved in EAOC progression remain largely unknown, hindering the development of preventative strategies, screening tools and effective therapeutics. Methodology In this unique longitudinal cohort of endometriosis patients, 5 tissue groups were defined. The study groups contained tissue from patients with endometriosis who developed EAOC and included endometriosis prior to EAOC (group 1), clear cell carcinoma (CCC) or endometrioid carcinoma (EC) (2) and concurrent endometriosis (3). The control groups contained endometriosis without EAOC association (4) and healthy uterine adnexal tissue (5). RNA, extracted from paraffin-embedded tissue blocks, underwent gene expression profiling with the Nanostring IO360 panel. Results Overlapping expression levels were seen amongst the endometriosis subgroups, with small oncogenic changes in concurrent endometriosis. Compared to adnexal tissue, both endometriosis and EC had higher expression levels of genes involved in myeloid and lymphoid cell compartments. Meanwhile, endometriosis and adnexal tissue, compared to EAOC, demonstrated higher levels of genes in signaling pathways such as MAPK, PI3K-Akt, TGF-β, and Wnt. Additionally, compared to CCC, the EC samples had lower expression of genes involved in angiogenesis, but higher levels antigen presentation and the lymphoid cell compartment. Conclusion No factors were identified that can identify patients at risk for EAOC prior to tumor development. Both endometriosis and EC had a more inflamed signature compared to adnexal tissue and CCC. Carcinogenic changes in concurrent endometriosis may be due to the local tumor microenvironment, but need further investigation. Furthermore, the differences between the EAOC subtypes suggest distinct processes driving EC or CCC development from endometriotic lesions, with a more inflammatory signature in EC that may be promising for the development future therapeutic strategies. This study sheds light on immune dynamics in ovarian endometriosis and EAOC, offering potential avenues for future research. Disclosures The authors have nothing to disclose.