SYK expression in metastatic retinoblastoma.

Abstract

e13544 Background: Retinoblastoma is an aggressive childhood cancer of the retina. While more than 90% of patients are cured when tumor is confined to the globe, for up to half of children in developing countries with advanced tumor at diagnosis, retinoblastoma remains a lethal disease. Recent whole-genome sequencing demonstrated that the retinoblastoma genome is relatively stable (Zhang et al). However, RB1 loss is associated with epigenetic deregulation of several cancer pathways. Significantly, the proto-oncogene SYK, spleen tyrosine kinase, which has no role in normal eye development, is upregulated in retinoblastoma and required for tumor cell survival (Zhang et al). Immunohistochemical (IHC) studies showed that SYK is ubiquitously overexpressed in intraocular retinoblastoma, whereas it is absent in normal retina. The purpose of this study is to investigate whether SYK overexpression persists in metastatic retinoblastoma. Methods: From 1962-2011, seven metastatic retinoblastoma tumor specimens (excluding bone marrow or cerebrospinal fluid) from six retinoblastoma patients were retrieved from the Pathology Archives in our institution. Morphology and supportive IHC, to include immunopositivity for synaptophysin and immunonegativity for cytokeratins, confirmed the diagnosis of metastatic retinoblastoma in each case. IHC for SYK was performed according to the previously published technique (Zhang et al). Results: Tumors occurred in two male and four female patients with seven metastatic retinoblastoma samples in scalp, lymph node, neck, ovary and bone (femur). By IHC, all seven metastatic retinoblastoma tumor samples were positive for SYK. Conclusions: This is the first report of SYK overexpression in metastatic retinoblastoma. Drugs targeting SYK are already in clinical trials for adults with leukemia and rheumatoid arthritis, and preclinical efficacy in vitro and in vivo has been established. Moving from bench to bedside with this epigenetically targeted agent warrants further investigation.