Molecular Profiling of Endometrial Cancer From TCGA to Clinical Practice

Abstract

Molecular classification provides an objective, reproducible framework for categorization of endometrial cancers (ECs), informing prognosis and selection of therapy. Currently, the uptake of molecular classification, integration in to EC management algorithms, and enrollment in molecular subtype-specific clinical trials lags behind what it could be. Access to molecular testing is not uniform, and subsequent management (surgical, adjuvant therapy) is unacceptably variable. We are in the midst of a critical landscape change in this disease site, with increasing emphasis on the integration of molecular features in EC care that can potentially improve standard of care globally. This article summarizes the rationale for molecular classification of ECs, strategies for implementation in low and high resource settings, and actionable opportunities based on this information.

Metabolism pathway-based subtyping in endometrial cancer: An integrated study by multi-omics analysis and machine learning algorithms

“…Patients in the MPS3 cluster tended to be older compared to those in the MPS1/2 clusters (p = 0.082) ( Figure S2 C). Comparison of the TCGA molecular subgroups 34 with the MPS clusters revealed that the MPS3 cluster was predominantly composed of the CN-H type, whereas the MPS2 cluster demonstrated a higher proportion of the CN-L type (p < 0.001) ( Figure 2 F; Table S3 ). Subgroup analysis revealed that the largest subset of EC (referred to as the nonspecific molecular profile [NSMP], also known as CN-L) exhibited heterogeneous metabolic profiles across MPS clusters.…”

Letter to the Editor: Analysis of adjuvant therapy in early staged endometrioid endometrial cancer—FIGO 2023 classification

“…This appears to be consistent with the population of early-stage, thinner patients who typically experience worse clinical outcomes. 3,4 The clinical trial that has come closest to exploring adjuvant therapy is PORTEC-3, which included 37 Stage I endometrial cancer patients with a high risk (based on the ESMO 2016 classification), of whom 23 were in Stage IA. 5 However, according to the authors of the ESMO guidelines for endometrial cancer, the number of patients and events in this trial was too low to draw definitive conclusions about the efficacy of adjuvant therapy in different stages.…”

Recent Advances in Endometrial Cancer Management

“…In recent years, growing attempts have been carried out to improve the quality of care in the setting of gynecologic oncology, and, in particular, in endometrial cancer management [ 1 ]. Major advances included the introduction of even more sophisticated minimally invasive techniques and personalized treatments (including immune checkpoint inhibitors and targeted therapies) [ 2 , 3 , 4 ].…”

“…Major advances included the introduction of even more sophisticated minimally invasive techniques and personalized treatments (including immune checkpoint inhibitors and targeted therapies) [ 2 , 3 , 4 ]. Major advances in the field of endometrial cancer are the use of sentinel node mapping through the use of florescence-guided minimally invasive surgery, the adoption of molecular and genomic profiling, and the introduction of immunotherapy [ 1 , 5 , 6 ]. Sentinel node mapping has replaced lymphadenectomy in the surgical staging of endometrial cancer [ 7 , 8 ].…”

“…Although no specific data are available on the management of low-volume disease, the detection of isolated tumor cells and micrometastases provides important data regarding prognostication [ 10 ]. Furthermore, the introduction of molecular/genomic profiling would be useful in tailoring the most appropriate treatments [ 1 , 3 ]. In the advanced/metastatic setting, molecular characterization provides important information regarding the most appropriate treatments.…”