GPER and ERα expression in abnormal endometrial proliferations

Area of Science:

• Endocrinology
• Molecular Biology
• Gynecologic Oncology

Background:

• G-protein coupled estrogen receptor 1 (GPER) is an extranuclear estrogen receptor linked to genital malignancies.
• Estrogen receptor alpha (ERα) is primarily involved in the genomic actions of estrogens, regulating cell growth.

Purpose of the Study:

• To investigate GPER expression in normal and abnormal proliferative endometrium.
• To correlate GPER expression with ERα presence and endometrial lesion grade.

Main Methods:

• Immunohistochemical analysis of GPER and ERα expression in endometrial tissue samples.
• Quantification of receptor densities in epithelial and stromal cells.
• Comparison of expression levels across normal proliferative endometrium, simple and complex endometrial hyperplasia, atypical endometrial hyperplasia, and endometrial adenocarcinomas.

Main Results:

• GPER was predominantly cytoplasmic, while ERα was mainly nuclear.
• Both receptors showed higher densities in epithelial cells compared to stromal cells.
• Receptor densities decreased in the order: complex endometrial hyperplasia > simple endometrial hyperplasia > normal proliferative endometrium > atypical endometrial hyperplasia, with ERα consistently higher.
• Endometrial adenocarcinomas exhibited significantly lower and more variable ERα and GPER expression.
• The GPER/ERα ratio increased significantly in high-grade endometrial lesions.

Conclusions:

• Nuclear ERα mediates the primary genomic effects of estrogens on cell growth.
• ERα expression is elevated in normal and benign endometrial proliferations, decreasing in atypical and malignant cells.
• Cytoplasmic GPER likely influences cell proliferation through tyrosine kinase signaling pathways.
• ERα may induce GPER gene transcription in benign endometrial lesions.
• An increased GPER/ERα ratio in high-grade lesions indicates GPER's direct involvement in endometrial malignancy.