Identification of distinct molecular subtypes of uterine carcinosarcoma

Abstract

Uterine carcinosarcoma (UCS) is a rare but lethal neoplasm with high metastasis and recurrence rate, and to date, no molecular classification of UCS has been defined to achieve targeted therapies. In this study, we identified two distinct molecular subtypes of UCS with distinct gene expression patterns and clinicopathologic characteristics. Subtype I UCS recapitulates low-grade UCS, in contrast subtype II UCS represents high-grade UCS with higher tumor invasion rate and tumor weight. Interestingly, subtype I UCS is characterized by cell adhesion and apoptosis pathways, whereas genes over-expressed in subtype II UCS are more involved in myogenesis/muscle development. We also proposed certain potential subtype specific therapeutic targets, such as SYK (spleen tyrosine kinase) for subtype I and cell-cycle proteins for subtype II. Our findings provide a better recognition of UCS molecular subtypes and subtype specific oncogenesis mechanisms, and can help develop more specific targeted treatment options for these tumors.