Biomarkers Associated with Lymph Nodal Metastasis in Endometrioid Endometrial Carcinoma

SIMPLE SUMMARY: In endometrial cancer, lymph node invasion assessed through surgical lymphadenectomy or sentinel lymph node biopsy is a determinant factor for the prognosis and planification of adjuvant treatment. Those surgical procedures are associated with short- and long-term complications. Recent advances in molecular characterization of endometrial cancer have provided important insights into the biological nature of tumors but have not improved the pre-operative prediction of LND. This study is a description of the transcriptomic landscape associated with lymph node metastases in endometroid endometrial carcinomas. A 54-genes expression signature was generated at analysis of the primary tumor. Differential gene expression was found between patients with and without lymph node metastasis, with an 87% accuracy. Our findings provide a basis for the development of a gene expression-based signature that can be used to pre-operatively select patients for whom surgical assessment of lymph node status is of little value, and, consequently, an unfavorable risk–benefit balance. ABSTRACT: Introduction. Lymph node metastasis is determinant in the prognosis and treatment of endometrioid endometrial cancer (EEC) but the risk–benefit balance of surgical lymph node staging remains controversial. Objective. Describe the pathways associated with lymph node metastases in EEC detected by whole RNA sequencing. Methods. RNA-sequencing was performed on a retrospective series of 30 non-metastatic EEC. N+ and N− patients were matched for tumoral size, tumoral grade and myometrial invasion. Results. Twenty-eight EECs were analyzable (16 N+ and 12 N−). Bioinformatics Unsupervised analysis revealed three patterns of expression, enriched in N+, mix of N+/N− and enriched in N−, respectively. The cluster with only N+ patient overexpressed extra cellular matrix, epithelial to mesenchymal and smooth muscle contraction pathways with respect to the N− profile. Differential expression analysis between N+ and N− was used to generate a 54-genes signature with an 87% accuracy. Conclusion. RNA-expression analysis provides a basis to develop a gene expression-based signature that could pre-operatively predict lymph node invasion.