Protein expression and gene copy number changes of receptor tyrosine kinase in thymomas and thymic carcinomas

Ann Oncol. 2012 Dec;23(12):3129-3137. doi: 10.1093/annonc/mds147. Epub 2012 Jun 13.

Abstract

Background: Insulin-like growth factor-1 receptor (IGF-1R), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-type 2 (HER2), and c-Met are members of the receptor tyrosine kinases (RTKs). The associations between the RTK status [protein expression and gene copy number (GCN)] and patient characteristics and between the RTK status and prognosis remain undetermined.

Materials and methods: The study included 140 patients who underwent surgery for thymic tumors. Protein expression was evaluated by immunohistochemistry (IHC) and GCN was evaluated by bright-field in situ hybridization (BISH). The correlations between the RTK status and clinicopathological findings were examined.

Results: IGF-1R protein was frequently detected in thymic carcinoma (83.8%) and EGFR in thymic tumors (91.4%). Thirty-six and 39 tumors were BISH high for IGF-1R and EGFR, respectively: 28 and 25 exhibited high polysomy; 8 and 14 exhibited gene amplification. No tumor was positive for HER2 or c-Met by IHC and BISH. Multivariate analysis revealed that IGF-1R gene amplification (P = 0.027), thymic carcinoma histology, and higher tumor stage were significantly correlated with an adverse prognosis.

Conclusions: Thymic epithelial tumors frequently express IGF-1R and/or EGFR proteins. IGF-1R gene amplification is suggested to define an unfavorable subset for thymic epithelial tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • ErbB Receptors / genetics*
  • Female
  • Gene Dosage*
  • Gene Expression
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • In Situ Hybridization
  • Male
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / surgery
  • Proto-Oncogene Proteins c-met / genetics
  • Receptor, ErbB-2 / genetics
  • Receptor, IGF Type 1 / genetics*
  • Thymoma / genetics*
  • Thymoma / surgery
  • Thymus Neoplasms / genetics*
  • Thymus Neoplasms / surgery

Substances

  • Biomarkers, Tumor
  • EGFR protein, human
  • ERBB2 protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins c-met
  • Receptor, ErbB-2
  • Receptor, IGF Type 1

Supplementary concepts

  • Thymic epithelial tumor