Tropomyosin-related Kinase B Is Potentially a Biomarker of Prognosis and Therapeutic Target for Malignant Thymic Epithelial Tumors

Thymic epithelial tumors (TETs) mainly consist of thymoma and thymic carcinoma. Complete surgical resection is vital for the successful management of these TETs, and adjuvant therapy such as systematic chemotherapy and/or radiotherapy plays important roles in the management of recurrent or metastasized disease. However, there is still a lack of a standard treatment after the failure of these adjuvant therapies. There is thus a need to develop molecular targeted therapies for advanced malignant TETs. In the present study, we evaluated the biological significance of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling for TETs.The expression of TrkB in 48 formalin-fixed, paraffin-embedded TET specimens (43 thymoma and 5 thymic carcinoma) collected by surgical resection was evaluated immunohistochemically. A thymic carcinoma cell line was evaluated for the role of BDNF/TrkB signaling pathway in an in vitro assay.High TrkB expression was related to significantly poor prognosis in patients with TETs. In vitro experiments showed that BDNF/TrkB signaling was involved in the proliferation of Ty-82 cells, but not their invasion and migration.TrkB expression is a biomarker of the prognosis for TETs and the BDNF/TrkB signaling pathway is potentially a new therapeutic target for mTETs.