Insulin-Like Growth Factor-1 Receptor and Phosphorylated AKT-Serine 473 Expression in 132 Resected Thymomas and Thymic Carcinomas

BACKGROUND: Thymic malignancies are rare tumors. The insulin-like growth factor-1 (IGF-1)/IGF-1 receptor (IGF-1R) system is involved in the development of the thymus. IGF-1R expression in thymic epithelial malignancies is unknown. METHODS: The authors investigated the expression of IGF-1R and phosphorylated AKT serine 473 (p-AKT) by using immunohistochemistry and examined the clinicopathologic correlations in a retrospective, single-institution surgical series of 132 patients with thymic epithelial malignancies. RESULTS: Earlier disease stage, less aggressive histologic types, and complete resection were significant positive prognostic factors for disease-related survival and progression-free survival, and being a woman was a better prognostic factor for disease-related survival. IGF-1R and p-AKT protein levels were expressed in 20% and 36% of thymic tumors, respectively. Both markers were expressed more commonly in recurrent disease than in primary tumors, in more aggressive subtypes, and in more advanced disease stages. There was a trend toward better survival and progression-free survival in patients who were negative for IGF1R or p-AKT expression in the whole series. When only the 91 primary tumors, IGF1R expression was associated with worse progression-free survival (P<.001). CONCLUSIONS: The current retrospective analysis demonstrated that disease stage, tumor histology, sex, and resection type were major prognostic factors in the survival of patients with thymic malignancies. The expression levels of IGF-1R and p-AKT in thymic tumors suggested that IGF-1R is a potential target for treatment.

BACKGROUND: Thymic malignancies are rare tumors. The insulin-like growth factor-1 (IGF-1)/IGF-1 receptor (IGF-1R) system is involved in the development of the thymus. IGF-1R expression in thymic epithelial malignancies is unknown. METHODS: The authors investigated the expression of IGF-1R and phosphorylated AKT serine 473 (p-AKT) by using immunohistochemistry and examined the clinicopathologic correlations in a retrospective, single-institution surgical series of 132 patients with thymic epithelial malignancies. RESULTS: Earlier disease stage, less aggressive histologic types, and complete resection were significant positive prognostic factors for disease-related survival and progression-free survival, and being a woman was a better prognostic factor for disease-related survival. IGF-1R and p-AKT protein levels were expressed in 20% and 36% of thymic tumors, respectively. Both markers were expressed more commonly in recurrent disease than in primary tumors, in more aggressive subtypes, and in more advanced disease stages. There was a trend toward better survival and progression-free survival in patients who were negative for IGF1R or p-AKT expression in the whole series. When only the 91 primary tumors, IGF1R expression was associated with worse progression-free survival (P<.001). CONCLUSIONS: The current retrospective analysis demonstrated that disease stage, tumor histology, sex, and resection type were major prognostic factors in the survival of patients with thymic malignancies. The expression levels of IGF-1R and p-AKT in thymic tumors suggested that IGF-1R is a potential target for treatment. Cancer 2010; 116: 4686-95. Published 2010 by the American Cancer Society.