Upon closer examination of these 16 cases, nine had complete excision of the tumor and the remainder received CBR-5884 adjuvant therapy. More importantly, only two of the 16 patients had followup data for more than 5 years. These parameters could have resulted in the improved observed outcomes in these patients. Thus, the ability of the assay to accurately identify GW 501516 metastatic cases is likely to be higher than reflected in the current study. Furthermore, we confirmed that the signature was not significantly affected by intratumoral heterogeneity. The nine-gene signature is the first prognostic molecular signature that can accurately predict metastatic behavior in thymomas. It was particularly efficient at predicting which patients would not develop metastases; further studies need to be carried out to analyze whether these patients can be spared from adjuvant chemoradiation therapy. Among the nine genes included in the signature, three genes were upregulated in class 2 patients. These genes have been previously associated with invasion and metastasis or chemoresistance in multiple cancers, where they have been considered as potential therapeutic candidates. The signature is not dependent on proliferation as the genes do not belong to a proliferation metagene. The expression levels of AKR1B10 are low in IU-TAB-1 cell line, established by our group from a patient with stage II thymoma, WHO type AB. Further mechanistic studies, including knockin and knock-out approaches, are being undertaken to assess the therapeutic potential of these genes. The nine-gene signature not only could improve prognostication for all thymoma patients, but could also identify potential druggable targets for patients with high metastatic potential. The current retrospective study was based on multi-institutional samples from patients receiving different surgical and postsurgical treatments. Given the rarity of this disease, the initial surgical management, the assessment of extent of disease, and, in some cases, postoperative therapy was often provided at local centers prior to referral to the IUSCC. This can be considered a strength of the study as it permits generalization of the results to patients with thymomas and enables personalized management based on their risk. To date, no prospective surgical trial has been performed on thymoma, but this assay potentially allows stratification of patients with locally advanced disease into low- or high- risk categories with treatments assigned
