Dr Slomovitz on the Classification of Molecular Subtypes to Guide Treatment in Endometrial Cancer

Brian M. Slomovitz, MD, director, Gynecologic Oncology, co-chair, the Cancer Research Committee, Mount Sinai Medical Center, professor, Obstetrics and Gynecology, Florida International University, discusses the classification of molecular subtypes to guide treatment and care in endometrial cancers.

Utilizing The Cancer Genome Atlas (TCGA), investigators aimed to classify patients with endometrial cancer into 4 main risk groups by using a combination of immunohistochemistry and mutation analysis. This was done to better understand how to approach a patient’s treatment options, as certain disease characteristics are associated with a worse prognosis.

The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) identified 4 molecular subtypes: mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H); POLE mutated; copy-number low/p53 wild-type; and copy-number high/p53 mutated.

Nonspecific or copy-number low tumors generally consist of patients with low-grade endometrioid disease, and the majority do not classify as dMMR, Slomovitz continues. POLE mutations are relatively rare; however, they are associated with the best prognosis, and this group of patients is amenable to immunotherapy, Slomovitz explains. Additionally, patients with dMMR/MSI-H tumors are the most responsive to immunotherapy, Slomovitz notes.

As further information about the molecular characteristics of endometrial cancers is gathered, the attention paid to different biomarkers, such as p53 and estrogen receptor positivity, may shift, Slomovitz adds. By shifting away from histologic classifications of the tumors, it could allow for the classification of patients into 1 of the 4 risk subtypes, Slomovitz explains. In the 2023 International Federation of Gynecology and Obstetrics (FIGO) staging, it is expected that molecular classifications will be included for endometrial cancer, Slomovitz concludes.