Molecular testing for endometrial cancer: An SGO clinical practice statement

Area of Science:

• Oncology
• Genomics
• Molecular Pathology

Background:

• The Cancer Genome Atlas (TCGA) established four molecular subtypes of endometrial cancer with distinct prognoses.
• Accurate molecular classification is essential for personalized treatment strategies in endometrial cancer.

Purpose of the Study:

• To introduce the Proactive Molecular Classifier for Endometrial Cancer (PMCC) for cost-effective and accessible molecular subtyping.
• To guide clinicians in the testing, interpretation, and application of molecular information for endometrial cancer management.

Main Methods:

• Development of the Proactive Molecular Classifier for Endometrial Cancer (PMCC).
• Characterization of endometrial cancers into four molecular subtypes: POLE, mismatch repair deficient, p53 abnormal, and no specific molecular profile.
• Identification of additional molecular biomarkers (e.g., beta-catenin, Her2, PI3K/mTOR/AKT, L1CAM, hormone receptors, tumor mutational burden, ARID1A) influencing clinical behavior.

Main Results:

• The PMCC classifies endometrial cancers into four clinically relevant molecular subtypes.
• Prognostic significance of POLE and p53 status is highlighted, with potential future therapeutic implications.
• Numerous clinical trials are investigating subtype-specific treatments and targeted therapies based on molecular profiles.

Conclusions:

• Molecular classification is fundamental for guiding endometrial cancer treatment.
• Basic molecular testing, including mismatch repair deficiency assessment, should be standard practice.
• Understanding molecular biomarkers is key for optimizing patient outcomes and advancing targeted therapies in endometrial cancer.