ECE2016 Guided Posters Endocrine Tumours (10 abstracts)
Expression and mutational status of USP8 in tumours causing ectopic Cushing’s syndrome
Luis Gustavo Perez-Rivas 1 , Marily Theodoropoulou 1, , Andrea Oßwald 1 , Julia Fazel 1 , Masayuki Komada 3 , Thomas Kirchner 4 , Felix Beuschlein 1 & Martin Reincke 1
1Medizinische Klinik und Poliklinik IV, Ludwig-Maximilians-Universität München, Munich, Germany; 2Department of Endocrinology, Max Planck Institute of Psychiatry, Munich, Germany; 3Department of Biological Sciences, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan; 4Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany.
Introduction: Mutations activating USP8 have been detected in a high proportion of pituitary adenomas causing Cushing’s disease and have been linked to an increase of ACTH production in corticotroph cells. Whether USP8 mutations are involved in the tumorigenesis of the ectopic Cushing’s syndrome (ECS) caused by neuroendocrine tumors has not been studied.
Patients and methods: In this work we evaluate the role of USP8 in a series of 17 tumors from patients diagnosed with ECS by analyzing the expression of ACTH, EGFR and USP8 by immunohistochemistry, as well as the rate of mutations of USP8 using Sanger sequencing. USP8 expression was related to different clinical parameters and its action was studied in vitro.
Results: USP8 was found to be widely expressed in all examined tumors, although at different levels. Sanger sequencing did not detect heterozygous mutations in the USP8 gene. ACTH immunoreactivity was detected in 11/17 tumors (65%). The majority of ECS (12/17; 71%) had no or weak EGFR expression. No significant association was observed between USP8 immunoreactivity and clinical data, such as age, sex, BMI, hormonal levels or overall survival. Overexpressing USP8 and EGFR in the bronchial carcinoid cell line NCI-H727 – that does not synthesize ACTH – failed to trigger exogenous Pomc promoter activity.
Conclusions: Altogether these results suggest that, despite their role in pituitary tumors, neither USP8 nor EGFR are actively contributing to the ectopic production of ACTH.
Volume 41
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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