Abstract
Aneuploidy is a widely studied prognostic marker in endometrial cancer (EC), however, not implemented in clinical decision-making. It lacks validation in large prospective patient cohorts adjusted for currently standard applied prognostic markers, including estrogen/progesterone receptor status (ER/PR). Also, little is known about aneuploidy-related transcriptional alterations, relevant for understanding its role in EC biology, and as therapeutic target.We included 825 EC patients with available ploidy status and comprehensive clinicopathologic characterization to analyze ploidy as a prognostic marker. For 144 patients, gene expression data were available to explore aneuploidy-related transcriptional alterations.Aneuploidy was associated with high age, FIGO stage and grade, non-endometrioid histology, ER/PR negativity, and poor survival (p-values<0.001). In patients with ER/PR negative tumors, aneuploidy independently predicted poor survival (p=0.03), lymph node metastasis (p=0.007) and recurrence (p=0.002). A prognostic ‘aneuploidy signature’, linked to low expression of chromosome 15q genes, was identified and validated in TCGA data.In conclusion, aneuploidy adds prognostic information in ER/PR negative EC, identifying high-risk patients that could benefit from more aggressive therapies. The ‘aneuploidy signature’ equally identifies these aggressive tumors and suggests a link between aneuploidy and low expression of 15q genes. Integrated analyses point at various dysregulated pathways in aneuploid EC, underlining a complex biology.
Highlights
Aneuploidy, defined as an aberrant number of chromosomes, is a commonly observed feature in human cancers [1], including endometrial cancer (EC) [2]
Aneuploidy was significantly associated with well-established prognostic variables, including high age, FIGO stage and grade, non-endometrioid histology, and estrogen receptor and progesterone receptor (ER/PR) negativity (Table 1)
We found a similar pattern for cluster formation based on the nine genes: patients segregated into two distinct clusters, one ‘aneuploid cluster’ including 41% of the tumors, associated with a more aggressive phenotype, and one ‘diploid cluster’ including tumors with less aggressive features
Summary
Aneuploidy, defined as an aberrant number of chromosomes, is a commonly observed feature in human cancers [1], including endometrial cancer (EC) [2]. Aneuploidy is often evaluated in tumors as an indirect measure of chromosomal instability, and used as an indicator of poor outcome [3]. Ploidy status estimated by cytometric methods [11] has added prognostic information in several retrospective studies of EC, but has never been fully implemented in clinical treatment algorithms [12]. This is at least in part due to the lack of one common standardized method for measuring ploidy status in tumors [3]. Its clinical usefulness as prognostic marker, adjusted for clinical and histopathologic variables, lacks validation in large prospective patient cohorts [13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
