# Molecular Classification of Endometrial Carcinomas: Review and Recent Updates

## TL;DR

This paper reviews how molecular classification improves the understanding and treatment of endometrial cancer by integrating genomic data into clinical practice.

## Contribution

The paper emphasizes the clinical relevance of genomic biomarkers in refining diagnosis, prognosis, and targeted therapies for endometrial carcinoma.

## Key findings

- The TCGA project identified four molecular subtypes of endometrial carcinoma with distinct genomic alterations and clinical behaviors.
- Molecular classification correlates with differential patient outcomes and treatment responses, improving prognostic stratification.
- Integration of genomic biomarkers into clinical frameworks enhances diagnostic accuracy and personalized therapy.

## Abstract

Recent advances in elucidating the pathogenesis of endometrial carcinoma have highlighted the central role of cancer genomics in refining diagnostic classification, prognostic assessment, and therapeutic stratification. The integration of molecular classification into the latest World Health Organization (WHO) framework underscores the clinical relevance of genomic biomarkers in predicting patient outcomes and informing targeted therapeutic approaches. This review provides a comprehensive overview of the genomic landscape of endometrial carcinoma, emphasizing its significance in advancing precision and personalized medicine.

Endometrial carcinoma (EC) continues to represent a major cause of gynecologic cancer–related mortality among women worldwide. Its multifactorial etiopathogenesis and underlying molecular heterogeneity have been the focus of extensive investigation. While traditional histological classification provides essential diagnostic insight, it is limited in predicting prognosis and therapeutic response due to significant interobserver variability. Recent advances in molecular biology and cancer genomics have profoundly enhanced understanding of EC pathogenesis. The Cancer Genome Atlas (TCGA) project delineated four distinct molecular subtypes of EC, POLE ultra-mutated, microsatellite instability hypermutated (MSI-H), copy number low (CNL) and copy number high (CNH), each defined by unique genomic alterations, histopathologic features, and clinical behaviors. These molecular groups demonstrate significant prognostic and therapeutic implications, correlating with differential outcomes and treatment responses. This review summarizes current evidence on the genomic landscape of endometrial carcinoma and underscores the pivotal role of molecular classification in improving diagnostic accuracy, prognostic stratification, and personalized therapy. Ongoing research into molecular biomarkers holds promise for refining patient management and optimizing clinical outcomes.