Molecular classification of endometrial cancer of Chinese population.

Abstract

e17623 Background: Endometrial cancer (EC) is one of the most prevalent gynecologic tumors. Current diagnosis and treatment of EC no longer rely solely on traditional histopathological classification. Nevertheless, molecular classification of EC demonstrated clear prognostic value and may guide clinical decision. Methods: In this study, archived tissue specimens from 240 EC patients from Department of Pathology, Peking University People’s Hospital. Four subtypes [POLE ultramutated (POLE mut), microsatellite instability high (MSI-H), copy number low (CNL), and copy number high (CNH)] were stratified by next-generation sequencing (NGS) panel (Amoy Diagnostics, Xiamen, China) targeting POLE, TP53, BRCA1, and BRCA2 genes and microsatellite instability (MSI) status. Immunohistochemistry (IHC) was applied to detect the expression of P53, MMR and other related proteins. Results: Distribution of the EC subtypes in 240 patients was 13 (5.42%) of POLE mut, 36 (15.00%) of MSI-H, 41 (17.08%) of CNH, and 150 (62.50%) of CNL. Compared to published results of EC subtypes in Caucasian including TCGA, ProMisE as well as TransPORTEC, real-world data on Chinese ECs displayed a significantly larger proportion of CNL. In addition, novel biomarkers such as DUSP1, MCF7 and BUB1, which were independent prognostic marker from our previous research were validated. Also, it was found that BRCA2 appeared to be more prevalent in EC than BRCA1. Further analysis revealed that the overall consistency for NGS-based and IHC-based TP53 abnormalities detection and MSI/MMR status assessment were as high as 87.5% and 100%, respectively. Conclusions: Chinese ECs have unique molecular characteristics. In order to perform accurate molecular typing of Chinese ECs, more molecular indicators that match the characteristics of the Chinese population need to be added to the existing classifiers. NGS-based panel is easy to operate and replicate with high accuracy. Thus, it is a viable alternative to IHC in EC molecular classification.