Insulin-like growth factor-1 receptor expression in thymic malignancies

J Thorac Oncol. 2010 Sep;5(9):1439-46. doi: 10.1097/JTO.0b013e3181e392a8.


Introduction: Thymic epithelial tumors are rare mediastinal malignancies that can be invasive and difficult to treat. Insulin-like growth factor-1 receptor (IGF-1R) is a transmembrane receptor implicated in the regulation of cell metabolism, growth, and survival. As higher levels of IGF-1R protein expression may be associated with relative sensitivity to anti-IGF-1R antibody treatment, we investigated IGF-1R expression in thymic malignancies.

Methods: Sixty-three thymic tumors (56 thymomas and seven thymic carcinomas) were analyzed for total IGF-1R expression using immunohistochemistry with a specific antibody (clone G11, Roche-Ventana, Tucson, AZ). Expression levels were correlated with relevant clinical and pathologic variables, including epidermal growth factor receptor and KIT expression, and patient outcome.

Results: IGF-1R staining was negative in 13 (21%) cases, low (1+) in 20 (32%) cases, moderate (2+) in 20 (32%) cases, and high (3+) in 10 (16%) cases. Moderate to high IGF-1R staining was observed in 6 of 7 (86%) thymic carcinomas and in 24 of 56 (43%) thymomas (p = 0.039). Moderate to high IGF-1R staining was associated with high epidermal growth factor receptor staining (p = 0.015). By multivariate analysis, only tumor stage and histologic type were significant prognostic factors on time to progression (hazard ratio [HR] = 4.12, 95% confidence interval [CI]: 1.98-14.23; p = 0.010 and HR = 2.79, 95% CI: 1.62-12.50; p = 0.018, respectively). There was no association between IGF-1R expression and time to progression (HR = 3.07, 95% CI: 0.38-24.59; p = 0.291).

Conclusion: A majority of thymic malignancies display moderate to high expression of IGF-1R. The lack of preclinical models prevented us to further study the functional consequences of anti-IGF-1R therapy in this setting. However, given correlations in other cancers, these data support the evaluation of anti-IGF-1R inhibitors in thymic tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-kit / metabolism
  • Receptor, IGF Type 1 / metabolism*
  • Retrospective Studies
  • Survival Rate
  • Thymoma / metabolism*
  • Thymoma / pathology
  • Thymus Neoplasms / metabolism*
  • Thymus Neoplasms / pathology
  • Tissue Array Analysis


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