Immunohistochemical Analysis of PDGFR-α, PDGFR-β and c-Abl in Retinoblastoma: Potential Therapeutic Targets

Ophthalmic Res. 2016;55(3):159-62. doi: 10.1159/000442882. Epub 2016 Jan 14.

Abstract

Background: Our laboratory previously reported that imatinib mesylate (IM) has an inhibitory effect on two retinoblastoma (Rb) cell lines in vitro.

Aims: The purpose of this project was to determine the immunoexpression of platelet-derived growth factor receptor (PDGFR)-α, PDGFR-β and c-Abl in 61 human samples of Rb to determine if IM-sensitive receptors are present. Additionally, this paper seeks to establish a correlation between the expression of PDGFR, c-Abl and the histopathological prognosis.

Methods: Sixty-one paraffin-embedded Rbs were collected from the Henry C. Witelson Ocular Pathology Registry. PDGFR-α, PDGFR-β and c-Abl immunostaining was performed according to the protocol provided by Ventana Medical System Inc. Immunoreactivity was correlated with the presence or absence of invasion into the choroid and optic nerve.

Results: Overall, c-Abl expression was identified in 50 out of 61 specimens (81.97%), PDGFR-α was identified in 20 out of 60 specimens (33.33%) and PDGFR-β expression was identified in 57 out of 61 specimens (93.44%). Histopathological prognosis was not correlated with immunoreactivity except in the case of PDGFR-β.

Conclusions: Rb is a cancer that expresses PDGFR-α, PDGFR-β and c-Abl, which are known targets of IM. These markers may be responsible for the documented therapeutic effect of IM on Rb cell lines.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Child, Preschool
  • Female
  • Humans
  • Imatinib Mesylate / pharmacology
  • Immunohistochemistry
  • Infant
  • Male
  • Protein Kinase Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-abl / metabolism*
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism*
  • Receptor, Platelet-Derived Growth Factor beta / metabolism*
  • Retinal Neoplasms / metabolism*
  • Retinal Neoplasms / pathology
  • Retinoblastoma / metabolism*
  • Retinoblastoma / pathology

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • Imatinib Mesylate
  • Receptor, Platelet-Derived Growth Factor alpha
  • Receptor, Platelet-Derived Growth Factor beta
  • Proto-Oncogene Proteins c-abl