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Ditsch, Nina; Heublein, Sabine; Jeschke, Udo; Sattler, Cornelia; Kuhn, Christina; Hester, Anna; Czogalla, Bastian; Trillsch, Fabian; Mahner, Sven; Engel, Jutta; Mayr, Doris; Schmoeckel, Elisa (2020): Cytoplasmic versus nuclear THR alpha expression determines survival of ovarian cancer patients. In: Journal of cancer research and clinical oncology, Vol. 146, No. 8: pp. 1923-1932
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PURPOSE Thyroid hormone receptors (THR) have manifold functions and are involved in the carcinogenesis of several tumor types. Within this study, we aimed to investigate the expression pattern (nuclear versus cytoplasmic) of the THR alpha and its impact on patients survival in ovarian cancer (OvCa). METHODS The presence of the thyroid hormone receptors THR\textgreeka, THR\textgreeka1 and -~2 was investigated in 156 ovarian cancer samples using immunohistochemistry (IHC) using semi-quantitative immunoreactivity (IR) scores and correlated with clinical, pathological data, subtype of ovarian cancer, clinical data, staining of 20 already described OvCa marker proteins and overall survival (OS). RESULTS Among all subtypes of OvCa, clear cell carcinomas showed the highest THR\textgreeka expression. Furthermore, nuclear THR\textgreeka was associated with a reduced survival in this subtype. However, nuclear expressed THR\textgreeka1 turned out to be a positive prognosticator for all subtypes of OvCa patients. Nuclear THR\textgreeka2 is a positive prognosticator for OvCa patients of the serous subtype. In contrast, cytoplasmic expression THR\textgreeka2 was associated with a reduced OS in all subtypes of OvCa patients; while, cytoplasmic expression of THR\textgreeka1 is associated with reduced OS in mucinous OvCa patients only. In addition, THR\textgreeka expression correlates with gonadotropin receptors, steroid hormone receptors, TA-MUC1 and glycodelin. CONCLUSION Depending on nuclear or cytoplasmic expression, our study shows that THR\textgreeka and its isoforms 1 and 2 provide different prognostic information for ovarian cancer patients. Further investigations should analyze if THRs may represent new endocrine targets for the treatment of ovarian cancer.