Abstract

Background: Despite the fact that retinoblastoma treatment has dramatically increased the survival and vision preservation in these patients, it is still important to pursue new therapeutic targets to minimize the side-effects of current therapies. Gonadotropin releasing hormone (GnRH) has been shown to exert a direct anti-proliferative effect on many types of malignancies, such as breast cancer, skin melanoma, and glioblastoma. The aim of this study is to describe the presence of GnRH receptor (GnRHR) in retinoblastoma in order to identify a possible new therapeutic target for this disease. Methods: Protein expression of GnRHR was studied by immunohistochemistry in 32 eyes with retinoblastoma and in the Y79 retinoblastoma cell line. Expression was scored according to intensity (1-3) and distribution (1-4), which were multiplied to generate an immunoreactive score (IRS). A score of 1 to 6 was considered low, while scores higher than 6 were considered high. The Fisher’s exact test was used to compare GnRHR IRS with presence or absence of each morphological high-risk feature. Results: GnRHR was expressed in all retinoblastoma cases and in the Y79 cell line. High, and low expression according to IRS score was evident in 62.5% and 37.5% of cases. There were no differences in GnRH IRS with respect to uni- versus multi-focal tumors, type of growth (mixed/endophytic), rosette formation, choroidal invasion, extraocular extension orextension to the sclera, or optic nerve invasion. Conclusion: GnRHR is expressed in varying degrees in all retinoblastomas. Therefore, GnRHR may be a novel therapeutic target for the treatment of retinoblastoma. Moreover, GnRHR expression could be a biomarker for the responders. Nevertheless, GnRHR expression did not correlate with morphological prognostic factors in this series. Further studies with a larger number of cases and follow up are needed to confirm our results.

Keywords: Retinoblastoma; Gonadotropin release hormone receptor; AN-152