Spatial distribution of LGR5 expression in normal, ectopic, and neoplastic human endometrium

Area of Science:

• Gynecology
• Stem Cell Biology
• Molecular Pathology

Background:

• Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a known stem cell marker in various epithelial tissues.
• The precise location and function of LGR5 in normal and diseased human endometrium require further clarification.

Purpose of the Study:

• To investigate the spatial distribution and biological significance of LGR5 in the human endometrium.
• To analyze LGR5 expression patterns in normal endometrium, adenomyosis, endometriosis, endometrial hyperplasia, and endometrioid carcinoma.

Main Methods:

• RNA in situ hybridization was employed to assess LGR5 expression on tissue microarrays.
• Immunohistochemistry was used to evaluate associations with ARID1A loss, β-catenin nuclear expression, and mismatch repair deficiency.

Main Results:

• LGR5 expression was consistently enriched in the luminal epithelium of normal endometrium, with decreasing levels towards glandular regions.
• This topographic pattern was maintained in adenomyosis and endometriosis, with high expression in luminal-type epithelia.
• LGR5 expression in hyperplasia and endometrioid carcinoma showed variability but no significant difference from normal luminal epithelium; no association with ARID1A loss, β-catenin, or mismatch repair deficiency was found.

Conclusions:

• LGR5 exhibits a consistent spatial distribution in the human endometrium, primarily in the luminal epithelial compartment.
• No significant correlation was observed between LGR5 expression and major molecular alterations in endometrioid carcinoma.
• These findings establish LGR5 as a compartment-specific epithelial marker, laying groundwork for future functional research.