TCGA molecular subgroups and FIGO grade in endometrial endometrioid carcinoma

Background: International Federation of Gynecology and Obstetrics (FIGO) grade is a crucial factor in the current system for the risk stratification of endometrial endometrioid carcinoma (EC). The Cancer Genome Atlas (TCGA) demonstrated four molecular prognostic subgroups for EC: POLE (good prognosis), microsatellite-instable (MSI, intermediate prognosis), copy-number-high (CNH, poor prognosis), and copy-number-low (CNL, variable prognosis). Objective: To assess how the prevalence of the TCGA molecular subgroups changes from low-grade (G1-2) to high-grade (G3) EC, to understand how it may affect the current risk-assessment system. Methods: A systematic review and meta-analysis was carried out by searching seven electronic databases from January 2013 to September 2019 for studies assessing the TCGA classification G1–2 and G3 EC. Pooled prevalence of the TCGA subgroups was calculated in EC. The association of each subgroup with grade was assessed using odds ratio (OR), with a significant p value < 0.05. Results: Nine studies with 3185 patients were included. G3 EC showed significantly higher prevalence of the POLE subgroup (12.1% vs 6.2%; OR = 2.13; p = 0.0001), of the MSI subgroup (39.7% vs 24.7%; OR = 2.15; p = 0.0003) and of the CNH subgroup (21.3% vs 4.7%; OR = 5.25; p < 0.00001), and significantly lower prevalence of the CNL subgroup (28% vs 63.5%; OR = 0.2; p < 0.00001) than G1–2 EC. Conclusion: The prevalence of the TCGA subgroups is not in accordance with the prognostic value of FIGO grade, indicating that the current risk stratification of EC will be heavily affected by molecular signature.