LAUSR

OBJECTIVES The Cancer Genome Atlas-based molecular classification of endometrial carcinoma (EC) has the potential to better identify those patients whose disease is likely to behave differently than predicted when using traditional risk stratification, however, the optimal approach to molecular subtype assignment in routine practice remains undetermined. The aim of this study was to compare the results of two different widely available approaches to diagnosis of EC molecular subtype. METHODS EC from 60 patients, were molecularly subclassified using two different methods; by performing the FoundationOne CDx Next Generation Sequencing (NGS) panel and using the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) classifier and performing immunohistochemical stainings for MMR proteins and p53. POLE mutation status was in both settings derived from FoundationOne results. RESULTS Molecular classification based on ProMisE was successful for all 60 tumors. MSI status could be determined based on the NGS panel results in 53 of 60 tumors, so ProMisE and NGS molecular subtype assignment could be directly compared for these 53 tumors. Molecular subtype diagnosis based on NGS and ProMisE was in agreement for 52 of 53 tumors. One tumor was microsatellite stable (MSS) but showed loss of MLH1 and PMS2 expression. CONCLUSIONS Molecular subtype diagnosis of EC based on NGS panel sequencing of formalin-fixed paraffin-embedded endometrial carcinomas and based primarily on immunostaining (ProMisE) yield identical results in 98.1% (52/53, kappa - 0.97) of cases. While results are comparable using these two approaches, each has advantages and disadvantages that will influence the choice of method to be used in clinical practice.