Immunohistochemical expression of CD117 and vascular endothelial growth factor in retinoblastoma: possible targets of new therapies

Int J Clin Exp Pathol. 2014 Aug 15;7(9):5725-37. eCollection 2014.

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.

Keywords: CD117; VEGF; immunohistochemistry; retinoblastoma.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Chemotherapy, Adjuvant
  • Child, Preschool
  • Choroid / chemistry
  • Choroid / pathology
  • Drug Design
  • Eye Enucleation
  • Female
  • Humans
  • Immunohistochemistry*
  • Infant
  • Kaplan-Meier Estimate
  • Male
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness
  • Optic Nerve / chemistry
  • Optic Nerve / pathology
  • Predictive Value of Tests
  • Prospective Studies
  • Proto-Oncogene Proteins c-kit / analysis*
  • Retinal Neoplasms / chemistry*
  • Retinal Neoplasms / mortality
  • Retinal Neoplasms / pathology
  • Retinal Neoplasms / therapy
  • Retinal Vessels / chemistry
  • Retinal Vessels / pathology
  • Retinoblastoma / chemistry*
  • Retinoblastoma / mortality
  • Retinoblastoma / pathology
  • Retinoblastoma / therapy
  • Time Factors
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / analysis*

Substances

  • Biomarkers, Tumor
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Proto-Oncogene Proteins c-kit