Abstract
BACKGROUND: We aimed to compare the values of next-generation sequencing (NGS) and Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) in redefining the molecular classification of endometrial cancer (EC). METHODS: We investigated the relationship between clinical outcomes and molecular subtypes of POLE, microsatellite instability-high (MSI-H), copy number low (CN-L), and copy number high (CN-H) classified by cancer gene panel testing for 145 cancer-related genes, as well as the immunohistochemical status of p53 and mismatch repair genes, in 200 cases of EC. RESULTS: The NGS-based classification identified CN-L subtype as the most prevalent (104/200, 52.0%), followed by MSI-H (38/200, 19.0%), POLE (33/200, 16.5%), and CN-H (25/200, 12.5%). Overall survival differed significantly for the four subtypes based on the NGS (p = 0.006) but not on the ProMisE (p = 0.117) classification. Additional mutations were identified for some POLE subtypes beyond the known hotspots, with 18.2% (6 of 33) showing concurrent MSI-H. Immunohistochemistry showed a p53 wild-type pattern for 12 (48%) CN-H cases, and there was no significant difference in prognosis depending on the p53 status in the CN-H subtype. CONCLUSIONS: NGS surpassed ProMisE in EC molecular classification, offering precise stratification and prognostication. Our NGS platform has the potential to contribute to personalized treatment in EC.