The G protein-coupled estrogen receptor 1 (GPER/GPR30) does not predict survival in patients with ovarian cancer

Abstract

BackgroundEven though ovarian tumors are not generally considered estrogen-sensitive, estrogens may still have an impact on ovarian tumor progression. The recently identified trans-membrane estrogen receptor GPER is involved in rapid estrogen signaling. Furthermore, it binds selective estrogen receptor modulators with agonistic effect, which could explain tamoxifen controversies.MethodsGPER mRNA was assayed with quantitative real-time PCR (qPCR) in 42 primary ovarian tumors and 7 ovarian cancer cell lines. ERα and ERβ mRNA were analyzed for comparison. GPER protein was semi-quantified with densitometric scanning of Western blots and its tissue distribution analyzed with immunohistochemistry (IHC) in 40 ovarian tumors. In addition, IHC was evaluated in a tissue microarray (TMA) of 150 primary malignant ovarian tumors.ResultsAll tumor samples contained GPER mRNA. The content of mRNA was not different between benign and malignant tumors, but one third of malignant samples over-expressed GPER mRNA. The content of ERα mRNA was higher in malignant than in benign tumors, whereas ERβ mRNA was higher in benign than in malignant tumors. GPER mRNA was detected in all seven ovarian cancer cell lines with highest levels in TOV21G and TOV112D cells. Similar expression pattern was seen for ERβ mRNA. Western blot demonstrated GPER protein in all tumor samples. Semi-quantification showed no difference between benign and malignant tumors, but about one third of malignant samples over-expressed GPER protein. GPER staining was localized mainly in epithelial cells. In the TMA study we found no correlation between GPER staining and clinical stage, histological grade or patient survival.ConclusionsGPER mRNA as well as GPER protein is present in both benign and malignant ovarian tumor tissue. About one third of malignant tumors over-expressed both GPER mRNA and protein. This, however, correlated neither with histological or clinical parameters nor with patient survival.

GPER-1 acts as a tumor suppressor in ovarian cancer

“…Another plausible explanation of the controversial results is a difference in population studied. Interestingly, another research group has not found any correlation between GPER-1 expression on mRNA and protein level with clinical outcome of ovarian cancer patients [14]. It is to note that in this cohort of 150 patients GPER-1 was expressed in only one third, whereas in our cohort more than 80% of the invasive ovarian cancers expressed GPER-1.…”

“…Smith and co-workers have shown in 89 ovarian cancer patients that GPER-1 expression is associated with poor survival [13]. In contrast, Kolkova and co-workers have not found any correlation between GPER-1 expression and survival of 152 patients with ovarian cancer [14]. A third research group has found that GPER-1 expression predicts lower survival of 150 ovarian cancer patients only by co-expression with epidermal growth factor receptor (EGFR) [15].…”

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

“…Regarding EOC, Smith et al published that patients highly expressing GPER are characterized by a significantly poorer outcome [13]. Later, it was speculated that GPER may not be related to EOC patients' overall survival at all [19]. Only recently, several studies, including ours, revealed that GPER expression in EOC may be associated with a more favorable prognosis [9,20].…”

The Role of Endocrine G Protein-Coupled Receptors in Ovarian Cancer Progression

“…These in vitro studies provide strong evidence that GPER promotes ovarian cancer cell proliferation. However, a clinical study involving 40 ovarian cancer patients with higher GPER expression found no association between clinical stage, pathological stage, and survival time (29). Tissue specimens from 124 ovarian cancers, 35 benign tumors, and 35 low-malignant tumors revealed that GPER is downregulated in ovarian cancer and that elevated expression of GPER correlates with a longer survival time.…”