Leucine-Rich α-2-Glycoprotein-1 (LRG-1) Expression in Retinoblastoma

Purpose: Retinoblastomas' growth rate is dependent on their ability to induce neovascularization. Leucine-rich α-2-glycoprotein-1 (LRG-1) was recently reported to be upregulated in human retinal disease with neovascular pathology. The purpose of the study was to determine LRG-1 expression in human retinoblastoma and to correlate it with clinical and histopathologic parameters and to assess how its expression correlates with vascular endothelial growth factor (VEGF) expression. Methods: LRG-1 expression was immunohistochemically evaluated in 34 retinoblastoma sections. Immunofluorescence for LRG-1/VEGF-A, LRG-1/TGF-β1/CD31, and LRG-1/Ki67 was performed. Quantitative RT-PCR analysis for the expression of LRG-1 was also done. Results: LRG-1 was found to be extensively and robustly expressed in retinoblastoma tumors (88%) irrespective of the degree of invasiveness, differentiation, iris neovascularization, and anterior segment involvement. LRG-1 immunoreactivity was predominantly observed in the central tumor vasculature and in the surrounding rim of ischemia. The higher frequency of LRG-1 expression in the presence of optic nerve infiltration, vitreous seeding, and necrosis was not statistically significant. Colocalization was observed between LRG-1 and VEGF-A staining, and no difference in their counts was detected. Quantitative RT-PCR analysis showed that LRG-1 gene expression was significantly upregulated (4.8-fold increase, P = 0.01). Conclusions: LRG-1 was highly expressed in human retinoblastoma sections, thus providing new insights into the molecular mechanism of retinoblastoma pathogenesis, and suggests a possible new therapeutic target. LRG-1 is a novel oncogene-associated protein shown to be vital to the progression of human cancers. Inhibiting tumor vasculature is progressively evolving as a target in anticancer therapy.