br Conclusion br Conflict of interest br Acknowledgments Thi
Conflict of interest
Acknowledgments This work was supported by an NRF grant (2016R1A2B4011196) from the Korea Research Foundation.
Introduction Thymic epithelial tumors are rare, but they are the most common primary neoplasm of the thymus and of the anterosuperior mediastinum in adults. In 2015, the World Health Organization (WHO) published a new edition of the histological classification of thymic epithelial tumors, grouping them into seven subtypes: A, atypical variant of A, AB, B1, B2, B3, and thymic carcinoma (including various types) . Although all thymomas are malignant tumors in the new WHO classification, the heterogenous group of tumors do show an morphological and clinical spectrum, ranging from an indolent, nearly benign behavior to locally infiltrative behavior, even with metastasizing lesions. Thymic carcinoma accounts for approximately 22% of all thymic epithelial neoplasms, with squamous cell carcinoma being the most common type, accounting for approximately 70% of all cases . Among all thymoma subtypes, type B3 thymoma is the closest to thymic carcinoma. Both of these two tumor subtypes possess obvious malignant biological behavior; they are difficult to differentiate relying only on pathology morphology, especially when only small biopsy specimens are available. MUC1 is a transmembrane mucin consisting of a heavily O-glycosylated excellilar domain, a transmembrane domain, and a cytoplasmic tail of 72 ap4 . Recent studies indicated that MUC1 is expressed at high levels in many human neoplasms and plays an important role in tumor development and progression , . Glucose is a major energy source for cells, and glucose uptake and glycolytic metabolism are enhanced in cancer cells compared to normal ones , . Glucose transporter 1, or GLUT1, is the most common glucose transporter in humans. It is the first member of the 14 members of the mammalian facilitative glucose transporter family of passive carriers that function as an energy-independent system for transporting glucose down a concentration gradient . Studies have identified GLUT1 as a prognostic and diagnostic marker and it has been found to be associated with tumor progression and poor overall survival in various malignant tumors . Over-expressions of MUC1 and GLUT1 have been reported to be closely associated with poor outcome in various malignant tumors, including thymic tumors. However, the rarity of thymic epithelial tumors has so far prevented a large multicenter cohort study. The previous two available studies only included 12 cases of thymic carcinoma, 7 cases of type B3 thymoma  and 17 cases of thymic carcinoma, 5 cases of type B3 thymoma , respectively. Furthermore, the latter study included specimens obtained though core needle biopsy without adequate tissue .
Material and methods
Discussion Previously, Kojika et al.  have examined 49 markers for their use in differentiating thymic carcinomas from type B3 thymomas. And finally, they found seven markers with significantly higher positive rate in the thymic carcinomas, among which GLUT1 and MUC1 were included, with the sensitivity and specificity of 72% and 100%, and 25% and 100%, respectively. Furthermore, they claimed that a combination of GLUT1, CD5, and CEA enabled differentiation of thymic carcinoma with 91.6% sensitivity and 100% specificity. Hence, they recommend the use of GLUT1 as an additional marker for differentiating thymic carcinoma from type B3 thymoma. Similarly, we also found either MUC1 or GLUT1 had significant higher positive expression in thymic carcinoma than in type B3 thymoma and GLUT1 had higher sensitivity than MUC1. However, MUC1 exhibited higher specificity than GLUT1 in our study. Previously, GLUT1 was considered as a potential intrinsic marker of hypoxia, and has been found to be expressed in various tumors, such as breast and ovary carcinoma, renal cell carcinoma, lung carcinoma, and malignant melanomas , , , , . GLUT1 was found definitely expressed in the membrane and cytoplasm in the tumor cells, and GLUT1 staining appeared to be more intense near central areas of tumor nests and in tumor cells around blood vessels than in the peripheral areas for type B3 thymoma. Interestingly, Kojika et al. observed more intense GLUT1 staining in the central than in the peripheral areas in thymic carcinoma . In our study, we found GLUT1 expression to be significantly correlated with age, with higher expressions observed for patients aged 50 or older.