Expression of RAGE and HMGB1 in Thymic Epithelial Tumors, Thymic Hyperplasia and Regular Thymic Morphology

被引:28
作者
Moser, Bernhard [1 ]
Janik, Stefan [1 ]
Schiefer, Ana-Iris [2 ]
Muellauer, Leonhard [2 ]
Bekos, Christine [1 ,3 ]
Scharrer, Anke [2 ]
Mildner, Michael [4 ]
Renyi-Vamos, Ferenc [5 ]
Klepetko, Walter [1 ]
Ankersmit, Hendrik Jan [1 ,3 ]
机构
[1] Med Univ Vienna, Div Surg, Dept Thorac Surg, Vienna, Austria
[2] Med Univ Vienna, Dept Pathol, Vienna, Austria
[3] Med Univ Vienna, Christian Doppler Lab Diag & Regenerat Cardiac &, Vienna, Austria
[4] Med Univ Vienna, Dept Dermatol, Vienna, Austria
[5] Natl Inst Oncol, Dept Gen & Thorac Surg, Budapest, Hungary
关键词
GLYCATION END-PRODUCTS; MYASTHENIA-GRAVIS; SOLUBLE RECEPTOR; THERAPEUTIC TARGET; DENDRITIC CELLS; T-CELLS; PATHOGENESIS; THYMOMA; CLASSIFICATION; BLOCKADE;
D O I
10.1371/journal.pone.0094118
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Recently, a role of the receptor for advanced glycation endproducts (RAGE) in myasthenia gravis was described. RAGE and its ligand high mobility group box 1 (HMGB1) play key roles in autoimmunity and cancer. To test whether these molecules are involved in patients with thymic abnormalities we applied immunohistochemical analysis in 33 cases of thymic epithelial tumors, comprising 27 thymomas and 6 thymic carcinomas, and 21 nonneoplastic thymuses. Both molecules were detected in neoplastic epithelial cells: RAGE staining was most intense in WHO type B2 thymomas and thymic carcinomas (p<0.001). HMGB1 nuclear staining was strongest in A and AB, and gradually less in B1 = B2>B3> thymic carcinoma (p<0.001). Conversely, HMGB1 cytoplasmic staining intensities were as follows: A and AB (none), B1 (strong), B2 (moderate), B3 and thymic carcinoma (weak); (p<0.001). Fetal thymic tissue showed a distinct expression of RAGE and HMGB1 in subcapsular cortical epithelial cells which was found in 50% of myasthenic patients. Furthermore RAGE and HMGB1 were expressed in thymocytes, macrophages, Hassall's corpuscles, thymic medulla, and germinal center cells in myasthenic patients. Immunohistochemistry results were complemented by systemic measurements (immunosorbent assay): serum levels of soluble RAGE were significantly reduced in patients with epithelial tumors (p = 0.008); and in invasive tumors (p = 0.008). Whereas RAGE was equally reduced in thymic hyperplasia and epithelial tumors (p = 0.003), HMGB1 was only elevated in malignancies (p = 0.036). Results were most pronounced in thymic carcinomas. Thus, RAGE and HMGB1 are involved in the (patho-) physiology of thymus, as evidenced by differentiated thymic and systemic expression patterns that may act as diagnostic or therapeutic targets in autoimmune disease and cancer.
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页数:14
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