HER2/ERBB2 immunoreactivity in human retinoblastoma

G. M. Seigel, S. Sharma, Abigail S Hackam, Dhaval K. Shah

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Retinoblastoma (RB) is an ocular malignancy of early childhood. Although mutations in the Rb1 gene and expression of stem cell markers have been identified in RB, additional information on RB-specific alterations in signaling pathways and protein expression would be useful for the design of targeted RB therapies. Here we have evaluated the expression of HER2 (ERBB2) in RB. HER2 is a member of the epidermal growth factor family, which is overexpressed in breast, ovarian, gastric, colorectal, pancreatic, and endometrial cancers in a stratified manner. Overexpression and gene amplification of HER2 is associated with aggressive malignancies, accompanied by chemoresistance and poor outcomes. In this study, we present the first evidence of HER2 immunoreactivity in retinoblastoma, as shown by immunocytochemistry, flow cytometry, and western immunoblot, with validation by reverse transcription PCR (RT-PCR) in both RB cell lines and clinical RB tumors. Our results suggest that the HER2 protein expressed in RB is a truncated version that spares the trastuzumab binding site, while HER2 is not detected in normal ocular tissues. Our discovery of HER2 expression in RB may lead to innovative and targeted drug treatment options designed to spare the eye and preserve vision in RB patients.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalTumor Biology
DOIs
StateAccepted/In press - Nov 27 2015

Keywords

  • Drug target
  • ERBB2
  • HER2
  • Retinoblastoma
  • Target discovery
  • Targeted therapy

ASJC Scopus subject areas

  • Cancer Research

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