Kisspeptin is a 54 amino acid peptide, encoded by the anti-metastasis gene KiSS-1, that activates the G-protein-coupled receptor, GPR54. The kisspeptin/GPR54 system is critical to normal reproductive development. KiSS-1 gene expression is increased in the human placenta in normal and molar pregnancies. Circulating kisspeptin is dramatically increased in normal pregnancy but levels in gestational trophoblastic neoplasia (GTN) have not previously been reported. The objective of this study was to determine if plasma kisspeptin levels are altered in patients with malignant GTN.
Method: Thirty nine blood samples were taken from 11 patients with malignant GTN at presentation, during and following chemotherapy. A single blood sample was taken from normal female volunteers (n=11). Plasma kisspeptin immunoreactivity (-IR), human chorionic gonadotrophin (hCG), progesterone and oestradiol concentrations were measured. Reverse-phase FPLC chromatography was used to further analyze kisspeptin-IR extracted from plasma by Sep-Pak cartridge. This study was approved by the local Ethical Committee.
Results: Plasma kisspeptin-IR in healthy females was <2 pmol/l. Plasma kisspeptin-IR and hCG concentrations in patients with malignant GTN were elevated at presentation and fell during and following treatment with chemotherapy in each patient (mean plasma kisspeptin-IR: pre-chemotherapy 1363±1076 pmol/l vs post-chemotherapy <2 pmol/l, P<0.0001. Mean plasma hCG: pre-chemotherapy 227191±152354 U/l vs post-chemotherapy 2 U/l, P<0.0001)). Plasma kisspeptin-IR strongly positively correlated with plasma hCG levels (r2=0.99, P<0.0001). Plasma kisspeptin-IR showed significant positive correlations with circulating levels of progesterone (r2=0.92, P<0.0001) and oestradiol (r2=0.70, P<0.0001) as did hCG (r2 =0.89, P<0.0001 for progesterone and r2 =0.64, P<0.0001 for oestradiol). In each plasma extract the kisspeptin-IR eluted in a single peak corresponding to the elution position of synthetic kisspeptin-54.
Conclusion: Our results suggest that measurement of plasma kisspeptin-IR may be a novel tumor marker in patients with malignant GTN.
01 - 05 Apr 2006
European Society of Endocrinology