The G-Protein Coupled Estrogen Receptor (GPER/GPR30) in ovarian granulosa cell tumors

Introduction: Ovarian granulosa cell tumors (GCTs) comprise a rare entity of ovarian sex cord stroma tumors. In line with their putative cells of origin GCTs possess the ability to synthesize estrogen and are supposed to be responsive to gonadotropins (FSH/LH). We recently identified the G-protein coupled estrogen receptor (GPER/GPR30) to be regulated by LH and FSH and to be differentially expressed throughout ovarian follicle development. Thus, supposing a possible role of GPER in GCTs, this study aimed to analyze GPER in GCTs and whether GPER might be correlated with clinicopathological parameters.

Methods: FFPE tissue collected from 26 patients that had undergone surgery for a GCT between 1988 and 2009 was included in this study and stained for GPER. GPER immunoreactivity was quantified and correlated with main clinicopathological variables.

Results: GPER was identified in the majority of GCTs with tumor stroma staining negative. Interestingly, GPER positivity ranged from single cell staining to a uniform strong signal. There was no significant relation of GPER with tumor size, lymph node status, metastasis, overall survival or disease-free survival. In three cases both the primary tumor as well as its recurrence was analyzed and GPER immunoreactivity was at least doubled in the recurrent tumors of all the three cases.

Conclusion: Due to the fact that GPER is regulated by estrogens as well as gonadotropins, GPER may also be affected by endocrine therapies applied to GCT patients. Hence GPER might be considered as a confounder when assessing the efficacy of (anti-)hormone-based therapies in GCTs.