High-grade endometrial carcinomas: Morphologic spectrum and molecular classification.

Area of Science:

• Oncology
• Pathology
• Genomics

Background:

• High-grade endometrial carcinoma (HGEC) is a diverse group of cancers with varied morphology, genetics, and clinical behavior.
• Current morphologic classification aids prognostication but suffers from poor reproducibility and discordance between biopsy and surgical specimens.
• This heterogeneity limits precise patient management and treatment decisions.

Purpose of the Study:

• To review the pathologic diagnosis and differential diagnosis of HGEC.
• To introduce the four molecular subtypes of HGEC established by The Cancer Genome Atlas (TCGA) Research Network.
• To discuss the clinical significance and application of TCGA molecular classification in supplementing traditional histotyping.

Main Methods:

• Review of existing literature on HGEC histopathology and molecular classification.
• Analysis of The Cancer Genome Atlas (TCGA) Research Network data on endometrial cancer subtypes.
• Comparison of morphologic and molecular classification systems for HGEC.

Main Results:

• HGEC encompasses endometrioid, serous, clear cell carcinomas, and undifferentiated/dedifferentiated types and carcinosarcomas.
• TCGA identified four molecular subtypes: POLE-ultramutated, microsatellite unstable, copy number high, and copy number low.
• Molecular classification demonstrates superior risk stratification and interobserver reproducibility compared to histotyping.

Conclusions:

• Molecular classification by TCGA provides a more reliable method for risk stratification in HGEC.
• The POLE-ultramutated group has the best prognosis, while the copy number high group has the worst.
• TCGA molecular subtyping complements histopathology, improving diagnostic accuracy and guiding patient management.