Expression of insulin-like growth factor pathway proteins in rhabdomyosarcoma: IGF-2 expression is associated with

Shalini Makawita1, Michael Ho, Adam D Durbin

  • 1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.

Insights

Insulin-like growth factor 2 (IGF2) expression differs between rhabdomyosarcoma (RMS) subtypes. Higher IGF2 levels in embryonal RMS and translocation-negative alveolar RMS suggest it may aid in distinguishing RMS subtypes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Insulin-like growth factor (IGF) signaling is implicated in rhabdomyosarcoma (RMS) pathogenesis.
  • Differential gene expression within the IGF pathway may distinguish RMS subtypes.

Purpose of the Study:

  • To investigate the expression patterns of IGF1, IGF2, IGFBP2, IGF1R, and IGF2R in ERMS and ARMS.
  • To determine if IGF pathway gene expression can differentiate between RMS subtypes.

Main Methods:

  • Immunohistochemistry was used to analyze protein expression in 32 RMS tumors (24 ERMS, 8 ARMS).
  • Real-time RT-PCR was performed on RMS cell lines to assess IGF2 mRNA levels.
  • PAX3/FKHR fusion gene introduction into an ERMS cell line was utilized for in vitro analysis.

Main Results:

  • IGF2, IGFBP2, IGF1R, and IGF2R were frequently expressed, while IGF1 was largely negative.
  • IGF2 expression was significantly higher in ERMS compared to ARMS (P = 0.0003).
  • In ARMS, IGF2 positivity was restricted to PAX/FKHR translocation-negative tumors. In vitro studies confirmed IGF2 downregulation by PAX3/FKHR.

Conclusions:

  • IGF2 ligand expression is associated with translocation-negative RMS and may serve as a diagnostic marker for distinguishing subtypes.
  • The PAX3/FKHR fusion gene appears to inhibit IGF2 expression, as supported by in vitro findings.

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