The Kisspeptin and GPR54 ligand-receptor pair are associated with favorable prognosis and clear cell subtype in human ovarian carcinoma

B73

GPR54 is a G-protein coupled receptor that stimulates release of GnRH upon binding with its secreted ligands, the Kisspeptins. The Kisspeptins have also been credited with inducing an anti-metastatic phenotype in tumor cells in vitro. This study characterizes expression of Kisspeptin and GPR54 in clinical ovarian tumor samples using the immunohistochemical method on a tissue microarray (TMA). The TMA consisted of 518 early stage ovarian carcinomas, all with linked clinical outcome data and was scored using a staining intensity scale of 0 (negative), +1 (mild-moderate), and +2 (strong). For statistical analysis, strong staining cases were considered either Kisspeptin or GPR54 positive and designated as 1, while all other cases were considered negative and designated 0. Kisspeptin positive and GPR54 positive cases show a favorable prognosis in univariable disease specific survival (p=0.0023, p=0.0092), as well as in overall survival (p=0.0006, p=0.0002). Further, Kissspeptin is an independent marker for favorable prognosis is disease specific and overall survival (p=0.0046, p=0.0170), while GPR54 is independent in overall survival only (p=0.0303). Both Kisspeptin and GPR54 positive cases are strongly associated with the ovarian carcinoma clear cell subtype (p<0.0001, p<0.0001). In conclusion, GPR54, in concert with the Kisspeptins, is a potential first biomarker for clear cell ovarian cancer subtype.