期刊
ONCOIMMUNOLOGY
卷 9, 期 1, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2020.1756130
关键词
Cancer biomarkers; heat shock proteins; non-thymomatous myasthenia gravis; prognostic factors; thymic epithelial tumors
资金
- research laboratory ARGE Moser (FOLAB Chirurgie - Department of Surgery, Medical University Vienna)
- research laboratory ARGE Ankersmit (FOLAB Chirurgie - Department of Surgery, Medical University Vienna)
Background Thymic epithelial tumors (TETs) are rare malignancies with unique association to the autoimmune disease myasthenia gravis (MG). Heat shock proteins (HSPs) harbor great potential as cancer biomarkers and HSP inhibitors approach clinical cancer therapy. Methods To explore HSP pathophysiology, we assessed sera (immunoassays) and tissues (immunohistochemistry) of TETs (and thymic tissues) for HSP27, phosphorylated (p)HSP27, HSP70 and HSP90 alpha expression in 114 TETs and 26 non-thymomatous MG patients undergoing extended thymectomy. Results Serum concentrations of HSP90 alpha were significantly increased in patients with thymic carcinomas, thymomas, thymic neuroendocrine tumors and non-thymomatous MG compared to patients who underwent thymectomy revealing regular thymic morphology or controls. In thymoma patients, high serum HSP90 alpha represented a significantly worse prognostic factor for free-from-recurrence, and complete tumor resection led to decreased levels. The expression of HSP90 in nuclei and cytoplasm of tumor cells and non-neoplastic lymphocytes varied with WHO histological subtype. HSP90 was expressed in centroblasts of thymic germinal centers in MG patients. Higher pHSP27 serum concentrations were observed in seropositive MG and those not treated with steroids. Conclusions HSP data suggest high potential for HSPs as TET cancer biomarkers or as candidates for targeted therapy. Caution is warranted in TET patients with associated MG overexpressing HSPs.
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