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Master Thesis

Marqueurs moléculaires de l'envahissement ganglionnaire dans les carcinomes endométrioïdes de l'endomètre

Abstract : Introduction: lymph node metastasis is a key determinant of the prognosis and treatment of endometrioid endometrial cancer (EEC) but lymphadenectomy is associated with an increased risk of surgery related systemic morbidity and lymphoedema. Additional tools including molecular biomarkers are needed to select the women for whom complete surgical staging should be performed to adapt adjuvant therapy. Objective: in this study, we describe the differential pathway landscape associated with lymph node metastases in EEC after whole RNA sequencing. Methods: we conducted a retrospective study at Institut Bergonie, Bordeaux, France. Selected patients were treated for a non-metastatic EEC between 2010 and 2017; with pathological tissue available and lymph nodes evaluation performed. Slides of the 56 selected patients were reviewed by a gynecopathologist and EEC were matched 1:1 between N+ and N- according to definitive tumoral size, tumoral grade and myometrial invasion. Paraffin-Embedded (FFPE) tissue samples, after macrodissection of the areas of interest, were used for whole RNA-sequencing. Only tumoral tissues were used for extraction. Results: twenty-eight EEC were analyzable after RNA sequencing (16 N+ and 12 N-). Unsupervised analysis revealed 3 distinctive patterns of expression (one with only N+ patient, one enriched with mainly N- patients and one with a mix of patients). The cluster with only N+ patient tended to overexpress three specific pathways: Extra cellular Matrix (ECM), Epithelial to Mesenchymal (EMT) and Smooth Muscle Contraction (SMC). Curated unsupervised analysis of differentially expressed genes between N+ and N- patients permitted to generate a 54 genes signature with an accuracy of 80% in our population. Conclusion: this RNA-expression profile may provide a basis for further study to develop a potential gene expression-based signature that could pre-operatively assess lymph node invasion and plan adjuvant therapy without lymphadenectomy.
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https://dumas.ccsd.cnrs.fr/dumas-03388743
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Submitted on : Wednesday, October 20, 2021 - 3:51:02 PM
Last modification on : Tuesday, November 30, 2021 - 3:46:25 AM
Long-term archiving on: : Friday, January 21, 2022 - 8:13:18 PM

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Mathilde Mairé. Marqueurs moléculaires de l'envahissement ganglionnaire dans les carcinomes endométrioïdes de l'endomètre. Sciences du Vivant [q-bio]. 2021. ⟨dumas-03388743⟩

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