Insulin-like growth factor-1 receptor expression in thymic malignancies.
BACKGROUND
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).


CONCLUSIONS
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.
Girard
Nicolas
N
Human Oncology and Pathogenesis Program, Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York City, NY 10065, USA.
Teruya-Feldstein
Julie
J
Payabyab
Eden C
EC
Riely
Gregory J
GJ
Rusch
Valerie W
VW
Kris
Mark G
MG
Zakowski
Maureen F
MF
D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D013945:Thymoma / Q000378:metabolism* / Q000473:pathology; D013953:Thymus Neoplasms / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit; D017526:Receptor, IGF Type 1