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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
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Protein expression and gene copy number changes of receptor tyrosine kinase in thymomas and thymic carcinomas

T Mimae1, K Tsuta2, T Kondo3

  • 1Divisions of Pathology and Clinical Laboratories, Japan; Divisions of Pharmaco-Proteomics, Japan; Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|June 16, 2012
PubMed
Abstract

Insights

Insulin-like growth factor-1 receptor (IGF-1R) gene amplification is linked to poorer outcomes in thymic tumors. This study investigated receptor tyrosine kinase (RTK) status in 140 patients, finding frequent IGF-1R and EGFR expression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Receptor tyrosine kinases (RTKs) like IGF-1R and EGFR are crucial in cell signaling.
  • The prognostic significance of RTK status (protein expression and gene copy number) in thymic tumors is not well understood.

Purpose of the Study:

  • To investigate the associations between RTK status and clinicopathological characteristics in thymic tumors.
  • To determine the prognostic value of RTK status in patients with thymic tumors.

Main Methods:

  • Protein expression of IGF-1R, EGFR, HER2, and c-Met was assessed using immunohistochemistry (IHC) in 140 thymic tumor samples.
  • Gene copy number (GCN) was evaluated by bright-field in situ hybridization (BISH).
  • Correlations between RTK status, patient characteristics, and prognosis were analyzed.

Main Results:

  • High protein expression of IGF-1R (83.8%) and EGFR (91.4%) was frequently observed.
  • IGF-1R and EGFR gene amplification or high polysomy were detected in a significant subset of tumors.
  • No HER2 or c-Met expression was found.
  • Multivariate analysis identified IGF-1R gene amplification, thymic carcinoma histology, and higher tumor stage as predictors of adverse prognosis.

Conclusions:

  • Thymic epithelial tumors commonly exhibit IGF-1R and/or EGFR protein expression.
  • IGF-1R gene amplification may identify a subset of thymic epithelial tumors with a poorer prognosis.

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