title: Immunohistochemical expression of CD117 and vascular endothelial growth factor in retinoblastoma: possible targets of new therapies.
abstract: CD117 (C-kit) is thought to play an important role in tumourigenesis. There are limited data in the literature concerning C-kit expression in retinoblastoma. To date, no immunohistochemical studies have been performed to assess the possible association of C-kit with vascular endothelial growth factor (VEGF) in retinoblastoma. This study was designed to investigate C-kit and VEGF immunoexpression in retinoblastoma, their relationship with prognostic parameters as well as the correlation between them. A prospective immunohistochemical study was conducted on 56 retinoblastoma cases. Patients who had received preoperative chemotherapy were excluded. Positive C-kit and VEGF immunoreactivity was observed in 48.2% and 76.8% of retinoblastoma cases respectively. No C-kit immunostaining was seen in the adjacent uninvolved retina. However, VEGF expression was detected within its vasculature. Retinoblastomas with combined pattern of tumour growth revealed a highly significant positive C-kit expression (P = 0.002) compared to cases with endophytic or exophytic growths. Also, positive C-kit expression was statistically higher in cases with optic nerve invasion (P = 0.001) and choroidal invasion (P ≤ 0.01) compared to negative cases. A highly significant positive VEGF expression was detected in cases with optic nerve invasion (P = 0.013) compared to negative cases. Moreover, a highly significant positive correlation was detected between C-kit and VEGF expression (P = 0.006). C-kit is a feature of more aggressive retinoblastomas, with increased expression in tumours spreading beyond the retina. Moreover, VEGF is vastly expressed in retinoblastoma and is associated with optic nerve invasion. Both C-kit and VEGF may represent potential therapeutic targets for retinoblastomas.
authors.affiliation: Department of Pathology, Faculty of Medicine, Ain Shams University Abbasseya square, Cairo, Egypt.
authors.forename: Nermeen S
authors.initials: NS
authors.lastname: Youssef
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Ain Shams University Abbasseya square, Cairo, Egypt.
authors.forename: Azza M
authors.initials: AM
authors.lastname: Said
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D017024:Chemotherapy, Adjuvant; D002675:Child, Preschool; D002829:Choroid / Q000737:chemistry / Q000473:pathology; D015195:Drug Design; D015353:Eye Enucleation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D009900:Optic Nerve / Q000737:chemistry / Q000473:pathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis*; D019572:Retinal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D012171:Retinal Vessels / Q000737:chemistry / Q000473:pathology; D012175:Retinoblastoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019009:Proto-Oncogene Proteins c-kit
keywords: CD117; VEGF; immunohistochemistry; retinoblastoma