Gonadotropin-Releasing Hormone Receptor II in Rare Ovarian Neoplasms: Correlation with VEGF and Clinicopathological Features

Pages 24-31

Agil Wahyu Wicaksono¹, Kiky Martha Ariesaka² and Muhammad Ary Zucha^3,4*

¹Division of Biomedical Science, Faculty of Medicine, Institute Pertanian Bogor, Bogor, Indonesia; ²Department of Medicine, Faculty of Medicine, Universitas Negeri Malang, Malang, Indonesia; ³Division of Oncology Gynecology, Department of Obstetrics and Gynecology, Universitas Gadjah Mada, Yogyakarta, Indonesia; ⁴Division of Oncology Gynecology, Department of Obstetrics and Gynecology, Universitas Padjadjaran, Bandung, Indonesia

Abstract: Background: Rare ovarian tumors pose diagnostic and therapeutic challenges due to their heterogeneous biology and limited treatment options. Gonadotropin-releasing hormone receptor type II (GnRHR-II) has been implicated in tumor regulation, including potential roles in angiogenesis, yet its clinicopathological significance in rare ovarian tumors remains unclear. This study aimed to evaluate GnRHR-II expression and its association with vascular endothelial growth factor (VEGF) as an angiogenic marker.

Methods: This analytical observational study used a cross-sectional design on tissue microarray samples containing 29 rare ovarian tumors, of which 25 were eligible for analysis. Immunohistochemistry was performed to assess GnRHR-II and VEGF expression, quantified using the H-score method. Associations with clinicopathological pa rameters were analyzed using t-test, ANOVA, Fisher’s exact test, and Pearson’s correlation, with p < 0.05 consid ered significant.

Results: The mean age of patients was 40.12 ± 19.73 years, with most cases diagnosed at stage I (72%) and classified as malignant (68%). GnRHR-II was consistently expressed across histopathological subtypes, with a mean H score of 187.50 ± 84.86, while VEGF showed a mean H-score of 103.35 ± 76.94. VEGF expression significantly correlated with tissue type (p = 0.004), being lowest in borderline tumors. There was positive expression of GnRHR II in rare ovarian cancer. However, correlation analysis revealed no significant relationship between GnRHR-II and VEGF (p = 0.541), indicating independent signaling pathways.

Conclusion: GnRHR-II is widely expressed in rare ovarian tumors but does not correlate with angiogenesis as reflected by VEGF expression. These findings suggest that GnRHR-II may act independently of VEGF-driven path ways, potentially serving a role in tumor biology distinct from angiogenic regulation. Further studies are warranted to explore its functional and therapeutic implications.

Keywords: Gonadotropin-releasing hormone receptor ii; rare ovarian tumor; angiogenesis; vascular endothelial growth factor; immunohistochemistry.