Expression of ERAlfa, its ERAlfaTrangle3 Splice Variant and Gama-SYNUCLEIN in Ovarian Cancer: A Pilot Study

Aims: Ovarian cancer has the highest mortality of any gynaecological malignancy; this is due to rapid peritoneal spread of tumour cells and neovascularization. Understanding the mechanisms underlying this is critical to developing early diagnostic or treatment strategies. We devised a pilot study to examine the role of g-SYNUCLEIN (g-SYN), oestrogen receptor (ER)a, and the splice variant ERaΔ3. Methodology: With ethical approval, ovarian tissue was collected from patients (n=24) undergoing oopherectomy for non-ovarian pathology or primary surgery for suspected ovarian cancer. Quantitative gene expression analysis was employed for g-SYN, ERa, and ERaΔ3. To identify the in situ localization, immunofluorescence for g-syn was carried out. Results: Ovarian tumour tissue exhibited an elevated expression of g-SYN and high-grade tumours had an elevated ERaΔ3:ERa ratio compared with benign tissue. The majority of previous studies point to the g-syn protein being present in epithelial cells of high-grade disease. Our study supports this, but additionally we conclusively identify its presence in the endothelial cells of vasculature surrounding low-grade disease; immunofluorescence was strongest in the apical cells surrounding the lumen. Conclusion: Our results demonstrate for the first time that there are readily-expressed levels of g-SYN and ERaΔ3 in normal ovarian tissue and ovarian tumours. In high-grade disease, g-syn and an elevated ERaΔ3:ERa ratio might confer metastatic potential to the tumourigenic cells and promote neoangiogenesis. Future in vitro studies might be necessary to delineate such a mechanism, which could potentially be the basis of early intervention.