Endometrial Stem/Progenitor cell (ES/PC) Marker Expression Profile in Adenosarcoma and Endometrial Stromal Sarcoma

Area of Science:

• Gynecologic Oncology
• Stem Cell Biology
• Cancer Genomics

Background:

• The uterus relies on endometrial stem/progenitor cells (ES/PCs) for homeostasis.
• ES/PCs reside in the endometrial stroma, the origin of adenosarcoma and endometrial stromal sarcoma (ESS).
• SUZ12 or DICER1 gene alterations in some tumors suggest a link to stem cell biology, but ES/PC involvement is unknown.

Purpose of the Study:

• To investigate the immunophenotypic resemblance of uterine tumors (ESSs and adenosarcomas) to ES/PCs.
• To determine if ES/PC marker expression has prognostic value in these tumors.
• To explore potential genetic drivers, including miRNA profiles in relation to DICER1 mutations.

Main Methods:

• Assessed expression of 11 ES/PC markers and 3 mature stromal proteins in 60 uterine tumors.
• Utilized unsupervised hierarchical clustering for protein expression profiling.
• Analyzed miRNA expression in adenosarcomas with/without DICER1 mutations.

Main Results:

• Tumors showed variable ES/PC marker expression and limited resemblance to ES/PCs.
• ES/PC marker clustering was prognostic for overall and disease-free survival in ESSs.
• DICER1 mutation status correlated with varied miRNA profiles and dysregulated pathways in adenosarcomas.

Conclusions:

• ESSs and adenosarcomas display diverse immunophenotypic similarities to ES/PCs.
• Tumor expression profiles offer prognostic insights.
• These findings may be influenced by underlying genetic alterations.