GPER and ERalpha expression in abnormal endometrial proliferations

Vol. 57 No. 2 Suppl., 2016
This supplement was not sponsored by Outside Organizations.


Andrei-Adrian Tica, Oana-Sorina Tica, Claudia Valentina Georgescu, Daniel Pirici, Maria Bogdan, Tudorel Ciurea, Stelian Stefanita Mogoanta, Corneliu Cristian Georgescu, Alexandru-Cristian Comanescu, Tudor-Adrian Balseanu, Raluca Niculina Ciurea, Eugen Osiac, Ana-Maria Buga, Marius Eugen Ciurea

G-protein coupled estrogen receptor 1 (GPER), a particular extranuclear estrogen receptor (ER), seems not to be significantly involved in normal female phenotype development but especially associated with severe genital malignancies. This study investigated the GPER expression in different types of normal and abnormal proliferative endometrium, and the correlation with the presence of ERalpha. GPER was much highly expressed in cytoplasm (than onto cell membrane), contrary to ERalpha, which was almost exclusively located in the nucleus. Both ERs densities were higher in columnar epithelial then in stromal cells, according with higher estrogen-sensitivity of epithelial cells. GPER and ERalpha density decreased as follows: complex endometrial hyperplasia (CEH) > simple endometrial hyperplasia (SHE) > normal proliferative endometrium (NPE) > atypical endometrial hyperplasia (AEH), ERalpha density being constantly higher. In endometrial adenocarcinomas, both ERs were significant lower expressed, and widely varied, but GPER/ERalpha ratio was significantly increased in high-grade lesions. Conclusions: The nuclear ERalpha is responsible for the genomic (the most important) mechanism of action of estrogens, involved in cell growth and multiplication. In normal and benign proliferations, ERalpha expression is increased as an evidence of its effects on cells with conserved architecture, in atypical and especially in malignant cells ERalpha s (and GPER s) density being much lower. Cytoplasmic GPER probably interfere with different tyrosine/protein kinases signaling pathways, also involved in cell growth and proliferation. In benign endometrial lesions, GPER s presence is, at least partially, the result of an inductor effect of ERalpha on GPER gene transcription. In high-grade lesions, GPER/ERalpha ratio was increased, demonstrating that GPER is involved per se in malignant endometrial proliferations.

Corresponding author: Oana-Sorina Tica, MD, PhD; e-mails:,

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Alexandru Marinescu, Alex Emilian Stepan, Claudiu Margaritescu, Alis Magdalena Marinescu, Roxana Eugenia Zavoi, Cristiana Eugenia Simionescu, Mihaela Niculescu

The incidence of cutaneous squamous cell carcinoma (CSCC) and its precursor lesions argues the research for validating markers that would define the biomolecular mechanisms behind the potential progression and aggressiveness of these lesions. In this study, we analyzed the expression of p53, p16 and Ki67 in 91 cases of CSCC and its precursors in relation with the histological prognostic parameters. The quantification of the immunohistochemical reactions indicated superior significant differences for the studied markers in squamous cell carcinomas compared to keratinocytic intraepithelial neoplasia (KIN). P16 and Ki67 immunostaining for Bowens disease were similar to those from poorly differentiated carcinomas. In this study, we found significant differences in p53 expression in relation to tumor grading and p16 expression in relation to tumor staging. Ki67 showed higher values in high-grade and advanced stage carcinomas. Positive reactions in preinvasive lesions as well as in CSCC support the sequential development and p53 and p16 involvement from the early stages of skin carcinogenesis.

Corresponding author: Alex Emilian Stepan, Lecturer, MD, PhD; e-mail:

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