Clinicopathological Profiles and Proliferative Activity of GnRH Receptor Type II Expressing Ovarian Cancer

Background: Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer, with high mortality and recurrence rates related to chemoresistance. The receptor of GnRH type II (GnRHR-II) is a more potent receptor of GnRH that may regulate proliferative capacity in peripheral tissues. Thus, it has the potential to serve as a novel therapy for malignancy. This study aimed to examine the clinicopathological profiles of epithelial ovarian cancer with GnRHR-II expression as well as the possible correlation between GnRHR-II and proliferative activity. Methods: We performed a cross-sectional study that included 30 epithelial ovarian cancer tissues embedded in a tissue microarray (TMA). The expression levels of GnRHR-II and Ki-67 were examined using immunohistochemistry and measured automatically using the ImageJ software. The association between GnRHR-II and Ki-67 expression levels was statistically tested. The correlation between GnRHR-II and Ki-67 expression was analyzed using Pearson's correlation, whereas the expression of GnRHR-II and Ki-67 in various clinicopathological conditions was analyzed using an unpaired t-test. Results: The mean age of epithelial ovarian cancer patients in this study was 51.87 ± 9.96 years. The mean H-Score of GnRHR-II was 62.52 + 28.96, while the mean H-Score of Ki-67 was 123.68 ± 57.72. We found that higher GnRHR-II expression was associated with a more advanced stage, lymph node metastases, and larger tumor size > T2 (p = 0.002, p = 0.035, p = 0.007, and p = 0.043, respectively). Interestingly, the expression levels of both GnRHR-II and Ki-67 were higher in the endometrioid type (p = 0.043 and p = 0.025, respectively), indicating the importance of this receptor in this histotype. However, the correlation between these two proteins was not statistically significant (p = 0.610). Conclusion: GnRHR-II expression was higher in patients with worse clinicopathological profiles, including more advanced stage, lymph node metastases, and larger tumor size. These results indicate that GnRHR-II may play an important role in ovarian cancer progression. Our findings broaden the potential of GnRHR-II as a novel therapeutic candidate for ovarian cancer treatment. © The Author(s) under exclusive licence to Association of Gynecologic Oncologists of India 2025.