AUTHOR=Li Ling , Chen Fangfang , Liu Jingcheng , Zhu Weifeng , Lin Liang , Chen Li , Shi Yi , Lin An , Chen Gang TITLE=Molecular classification grade 3 endometrial endometrioid carcinoma using a next-generation sequencing–based gene panel JOURNAL=Frontiers in Oncology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.935694 DOI=10.3389/fonc.2022.935694 ISSN=2234-943X ABSTRACT=

Over the past two decades, the incidence of endometrial cancer (EC) is increasing, and there is a need for molecular biomarkers to predict prognosis and guide treatment. A recent study from The Cancer Genome Atlas suggested to implement the EC analysis by molecular profile for improving diagnosis, prognosis, and therapeutic treatment. In this study, next-generation sequencing was performed on 70 cases of G3 endometrioid ECs (EECs) using an 11-gene panel (TP53, MLH1, MSH2, MSH6, PMS2, EPCAM, PIK3CA, CTNNB1, KRAS, PTEN, and POL) for molecular classification. The molecular classification based on the 11-gene NGS panel identified four molecular subgroups: POLE-ultramutated (n = 20, 28.6%), MSI-H (n = 27, 38.6%), NSMP (n = 13, 18.6%) and TP53mut (n = 10, 14.3%). The NGS method showed 98.6% (69 of 70 cases, kappa value 98%) in concordance with the cases assessed by immunohistochemistry (IHC). Among the seven dead cases, four were MSI-H tumors, two were TP53mut/p53abn tumors, and one was NSMP tumors with an average overall survival (OS) of 14.7 months. TP53mut subgroup showed that poor OS rates and POLE group have favorable prognosis. Our work suggested that the 11-gene panel is suitable for molecular classification in G3 EECs and for guiding prognosis and treatment decisions.