Gonadotropin-Releasing Hormone Receptor is expressed in Retinoblastoma

Abstract

Purpose: 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 therapy. Gonadotropin releasing hormone (GnRH) has been shown to exert a direct antiproliferative effect on many types of reproductive tissue cancers, 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 new possible 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). Low expression was considered an IRS score of 1 to 4, moderate 5 to 8, and high 9 to 12. GnRHR mRNA expression in Y79 cells were analyzed using reverse transcription polymerase chain reaction (RT-PCR). The Student's t-test was used to compare GnRHIRS cases with or without each morphological high risk features. Results: GnRHR was expressed in all retinoblastoma cases and in the Y79 cell line. There was no expression in normal ocular structures. High, moderate, and low expression according to IRS score was evident in 16%, 36%, and 48% of cases. There were no differences in GnRH IRS with respect to uni- versus multifocal tumors, type of growth (mixed/endophytic), rosette formation, choroidal invasion, extraocular extension or extension to the sclera, or optic nerve invasion. In Y79 cells, RT-PCR showed amplification of GnRHR mRNA. Conclusions: GnRHR is expressed in differing degrees in retinoblastomas, but did not correlate with prognostic factors of this particular tumor. Therefore, GnRHR may be a novel therapeutic target for the treatment of retinoblastoma. Further studies to analyze the response of the Y79 cell line to agonist and antagonist drugs are required to confirm the functionality of this receptor.