Endometrial carcinomas with ambiguous histology often harbor TP53 mutations

Area of Science:

• Gynecologic Oncology
• Molecular Pathology
• Genomics

Background:

• Endometrial carcinomas with ambiguous histology pose diagnostic challenges.
• Accurate molecular subtyping is crucial for predicting prognosis and guiding treatment.

Purpose of the Study:

• To characterize the molecular features of endometrial carcinomas with ambiguous histology.
• To correlate molecular profiles with clinical outcomes.

Main Methods:

• Analysis of mismatch repair (MMR) status, microsatellite instability (MSI) status, and whole-exome sequencing.
• Morphological and immunohistochemical evaluation.
• Clinical follow-up data collection.

Main Results:

• TP53 mutations were prevalent (78%), while pathogenic POLE mutations were absent.
• Eleven carcinomas (61%) were copy number high, and 7 (39%) were MSI-hypermutated.
• Mutations in MUC16, PIK3CA, and ARID1A were frequently observed.
• A significant proportion of patients experienced disease recurrence or mortality.

Conclusions:

• The molecular landscape of ambiguous endometrial carcinomas is characterized by TP53 mutations and absence of POLE mutations.
• These tumors exhibit heterogeneous molecular profiles and a high proportion are clinically aggressive.
• Molecular characterization is essential for understanding and managing these challenging endometrial cancers.