Identification of Distinct Molecular Subtypes of Endometrioid Adenocarcinoma

Abstract

Endometrial carcinoma (EC) is one of the most common gynecological cancers worldwide. Endometrioid adenocarcinoma (EAC) is the major form of EC, accounting for 75–80% of cases. Currently, there is no molecular classification system for EAC, so there are no corresponding targeted treatments. In this study, we identified two distinct molecular subtypes of EAC with different gene expression patterns and clinicopathologic characteristics. Subtype I EAC cases, accounting for the majority of cases (56%), were associated with an earlier stage, a more well-differentiated grade, a lower tumor invasion rate, and a more favorable prognosis, and the median tumor necrosis percent (15%) was also significantly higher in subtype I EAC. In contrast, subtype II EAC represents high-grade EAC, with a higher tumor invasion rate and tumor weight. The up-regulated genes in subtype I EAC were associated with the immune response, defense response, cell motion, and cell motility pathway, whereas the up-regulated genes in subtype II EAC were associated with the cell cycle, DNA replication, and RNA processing pathways. Additionally, we identified three potential subtype-specific biomarkers, comprising MDM2 (MDM2 proto-oncogene) for subtype I, and MSH2 (mutS homolog 2) and MSH6 (mutS homolog 6) for subtype II.