Primary cardiac sarcomas are rare and represent 20% of all primary cardiac tumors. Symptoms depend on the chambers and the cardiac structures involved. Transthoracic echocardiography is commonly used to identify a cardiac mass. The diagnosis of cardiac sarcoma requires adequate sampling and the careful use of ancillary diagnostic techniques. In the most recent histologic classification, angiosarcoma is the most common malignant tumor of the heart with recognizable differentiation. Undifferentiated sarcomas account for one-third of all cardiac sarcomas and have been incorporated in the malignant fibrous histiocytoma/pleomorphic sarcoma subgroup. Elective cardiac sarcoma therapy includes complete surgical excision when possible, followed by radio and chemotherapeutic regimen, the latter preferably containing anthracyclines, ifosfamide, or taxanes. Prognosis of cardiac sarcomas is very poor, with mean survival ranging from 9.6 to 16.5 months. A less-aggressive course seems related to the left atrium location, a low histologic grading with scarce cellular pleomorphism and low-mitotic activity, absence of necrosis, myxoid tumor appearance, and absence of metastasis at diagnosis.

Purpose The epithelial-mesenchymal transition (EMT) is emerging as a critical factor for the progression and metastasis of carcinomas, as well as drug resistance. The T-box transcription factor Brachyury has been recently characterized as a driver of EMT in human carcinoma cells. The purpose of this study was to characterize Brachyury as a potential target for lung cancer therapy. Experimental Design The expression of Brachyury was evaluated by PCR and by immunohistochemistry in human lung tumors and adult normal tissues. Brachyury gene copy number and promoter methylation status were analyzed in tumor tissues with various levels of Brachyury expression. Lung carcinoma cells’ susceptibility to T-cell lysis and EGFR kinase inhibition were also evaluated relative to the levels of Brachyury. Results Our results demonstrated Brachyury protein expression in 41% of primary lung carcinomas, including 48% of adenocarcinomas and 25% of squamous cell carcinomas. With the exception of normal testis and some thyroid tissues, the majority of normal tissues evaluated in this study were negative for the expression of Brachyury protein. Brachyury-specific T cells could lyse Brachyury positive tumors and the level of Brachyury corresponded to resistance of tumor cells to EGFR kinase inhibition. Conclusion We hypothesize that the elimination of Brachyury-positive tumor cells may be able to prevent and/or diminish tumor dissemination and the establishment of metastases. The ability of Brachyury-specific T-cell lines to lyse Brachyury-positive tumor cells, in vitro, supports the development of Brachyury-based immunotherapeutic approaches for the treatment of lung cancer.