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

Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a well-established stem cell marker in multiple epithelial tissues. However, its spatial distribution and biological relevance in normal and pathological human endometrium remain incompletely defined.

We analyzed LGR5 expression in normal proliferative and secretory endometrium, adenomyosis, endometriosis, endometrial hyperplasia, and endometrioid carcinoma using RNA in situ hybridization on tissue microarrays. Associations with ARID1A loss, β-catenin nuclear expression, and mismatch repair deficiency were evaluated by immunohistochemistry.

In normal endometrium, LGR5 expression was spatially compartmentalized, showing consistent enrichment in the luminal epithelium with decreasing expression toward functional and basal glandular regions across menstrual phases. This gradient was preserved in both proliferative and secretory endometrium. In adenomyosis and ovarian endometriosis, LGR5 remained highly expressed in luminal-type epithelial linings, recapitulating the topographic pattern observed in ectopic endometrium. In endometrial hyperplasia and endometrioid carcinoma, LGR5 expression demonstrated inter-sample variability but showed no significant differences compared with normal luminal epithelium. Furthermore, LGR5 expression was not associated with ARID1A loss, β-catenin dysregulation, or mismatch repair deficiency.

LGR5 expression in the human endometrium shows a consistent spatial distribution, with enrichment in the luminal epithelial compartment across normal, ectopic, and neoplastic conditions. No clear association was identified between LGR5 expression and key molecular alterations in endometrioid carcinoma. These findings support a descriptive role for LGR5 as a compartment-associated epithelial marker and provide a basis for future functional studies.