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Published in: Pituitary 4/2016

01-08-2016

A high-throughput analysis of the IDH1(R132H) protein expression in pituitary adenomas

Authors: Olivera Casar-Borota, Kristin Astrid Berland Øystese, Magnus Sundström, Linea Melchior, Vera Popovic

Published in: Pituitary | Issue 4/2016

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Abstract

Purpose

Inactivating mutations of isocitrate dehydrogenase (IDH) 1 and 2, mitochondrial enzymes participating in the Krebs tricarboxylic acid cycle play a role in the tumorigenesis of gliomas and also less frequently in acute myeloid leukemia and other malignancies. Inhibitors of mutant IDH1 and IDH2 may potentially be effective in the treatment of the IDH mutation driven tumors. Mutations in the succinate dehydrogenase, the other enzyme complex participating in the Krebs cycle and electron transfer of oxidative phosphorylation occur in the paragangliomas, gastrointestinal stromal tumors, and occasionally in the pituitary adenomas. We aimed to determine whether the IDH1(R132H) mutation, the most frequent IDH mutation in human malignancies, occurs in pituitary adenomas.

Methods

We performed immunohistochemical analysis by using a monoclonal anti-IDH1(R132H) antibody on the tissue microarrays containing specimens from the pituitary adenomas of different hormonal types from 246 patients. In positive samples, the status of the IDH1 gene was further examined by molecular genetic analyses.

Results

In all but one patient, there was no expression of mutated IDH1(R132H) protein in the tumor cells by immunohistochemistry. Only one patient with a recurring clinically non-functioning gonadotroph adenoma demonstrated IDH1(R132H)-immunostaining in both the primary tumor and the recurrence. However, no mutation in the IDH1 gene was detected using different molecular genetic analyses.

Conclusion

IDH1(R132H) mutation occurs only exceptionally in pituitary adenomas and does not play a role in their pathogenesis. Patients with pituitary adenomas do not seem to be candidates for treatment with the inhibitors of mutant IDH1.
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Metadata
Title
A high-throughput analysis of the IDH1(R132H) protein expression in pituitary adenomas
Authors
Olivera Casar-Borota
Kristin Astrid Berland Øystese
Magnus Sundström
Linea Melchior
Vera Popovic
Publication date
01-08-2016
Publisher
Springer US
Published in
Pituitary / Issue 4/2016
Print ISSN: 1386-341X
Electronic ISSN: 1573-7403
DOI
https://doi.org/10.1007/s11102-016-0720-7

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