Independent Tissue-Based Biomarkers in Endometrioid Endometrial Cancer: Tumor Budding in Microsatellite Instability and WHO Grading in Copy-Number-Low Patients

The molecular characterization of endometrial endometrioid adenocarcinomas has provided major advances in its prognostic stratification. However, risk assessment microsatellite instability (MSI) and copy-number (CN)-low cases remains a challenge. Thus, we aimed to identify tissue-based morphologic biomarkers that might help the stratification these cases. Histomorphologic parameters (WHO grading, tumor budding (TB), tumor–stroma ratio (as quantitative description stromal desmoplasia), tumor-infiltrating lymphocytes (TIL), “microcystic, elongated, fragmented” (MELF) pattern) were analyzed resection specimens TCGA-UCEC cohort (n = 228). For each parameter, two-tiered system was developed utilizing systematically determined cutoffs. Associations with survival outcomes calculated univariate multivariate analysis validated two independent cohorts. In MSI tumors, only TB remained an factor. (≥3 buds/high-power field) associated inferior lymph node metastases. significance confirmed validation CN-low established grading defined by WHO independently for high-grade tumors. evaluation identifying MSI-patients unfavorable prognosis who, e.g., could benefit from lymphadenectomy. WHO-based facilitates adenocarcinomas. Therefore, propose utilization easy-to-assess biomarkers, MSI/CN-low carcinomas improved clinical management.