P-325 Evidence for dysregulation of oncogene pathways at the gene expression level in the epithelium of deep infiltrating endometriosis compared to adenomyosis

Abstract Study question How does the gene expression profile of epithelium cells differ between deep infiltrating endometriosis (DIE) and adenomyosis (FA)? Summary answer The epithelial from DIE reveals a significant upregulation PI3K-pathway downregulation RAS-pathway compared to FA. What is known already Both FA, are histologically considered benign but have features malignant diseases, such as tendency for local tissue invasion. Recent next generation sequencing studies detected driver mutations in cancer-associated genes PIK3CA, ARID1A, PPP2R1A KRAS DIE, well Furthermore, identical were coexisting adenomyotic endometriotic lesions, supporting theory common molecular mechanism. differences these two entities therefore investigated present study. design, size, duration This an experimental analysis 7 19 samples (histologically confirmed), that formalin-fixed paraffin-embedded (FFPE) collected 2003 2018. These provided by bank National Centre Tumour Diseases (Heidelberg, Germany), accordance with Ethics Committee University Heidelberg (approval number S-362/2017). In addition, medical epidemiological data corresponding patients retrospectively analyzed based on clinical collected. Participants/materials, setting, methods For this study, epithelia FFPE microdissected laser-guided fashion. After RNA extraction, 770 was using nCounter Technology Human PanCancer Pathways Panel (Nanostring). All adjusted false discovery rate p < 0.05 fold change 0.66 or > 1.5 differentially expressed subjected functional annotation clustering DAVID bioinformatics resources. Main results role chance Our revealed total 162 genes, either significantly increased (n = 116) decreased 46) FA (with log2 changes p-value 0.05). Gene ontology KEGG pathway belonging focal adhesion pathway, pathways related viral infection, endocrine resistance, malignancy. upregulated mainly included RAS-pathway. Limitations, reasons caution average age lower, many them hormonally inactive due GnRH analogues, which mitigates any age-related differences. only relative studied groups without comparison normal endometrium. Overall, sample size relatively small further needed. Wider implications findings different signaling could, example, explain sensitivity diseases certain therapeutic approaches. While responds therapy progestogen dienogest, progesterone resistance often described patients. Trial registration not applicable