Tumor Heterogeneity in Endometrial Carcinoma: Practical Consequences

Area of Science:

• Oncology
• Pathology
• Genomics

Background:

• Endometrial carcinoma (EC) presents with intertumor and intratumoral heterogeneity.
• This heterogeneity involves diverse histologic types and varying morphologic/molecular features within a single tumor.

Purpose of the Study:

• To discuss the consequences of tumor heterogeneity in endometrial carcinoma.
• To illustrate morphologic and molecular heterogeneity using research examples.

Main Methods:

• Review of illustrative research examples of EC heterogeneity.
• Analysis of morphologic, molecular, and metabolomic data.
• Exome sequencing for branched evolution assessment.
• Evaluation of endometrial aspirates and hysterectomy specimens for heterogeneity detection.

Main Results:

• Morphologic heterogeneity observed in conventional and mixed EC types.
• Identification of EC with microsatellite instability.
• Evidence of branched evolution in tumor development.
• Distinct differences between tumor surface and invasion front (morphologic, molecular, metabolomic).
• Characterization of tumor microenvironment heterogeneity.
• Assessment of endometrial aspirates' sensitivity in detecting EC heterogeneity.
• Evaluation of sampling strategies for hysterectomy specimens.

Conclusions:

• Tumor heterogeneity in EC has significant clinical implications.
• Minor tumor cell populations can affect diagnosis, prognosis, and therapy.
• Effective detection strategies are essential for comprehensive patient care.