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A high-throughput analysis of the IDH1(R132H) protein expression in pituitary adenomas
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Oslo Univ Hosp, Dept Pathol, Sognsvannsveien 20, N-0372 Oslo, Norway..
Oslo Univ Hosp, Dept Specialised Endocrinol, Sognsvannsveien 20, N-0372 Oslo, Norway.;Univ Oslo, Fac Med, Klaus Torgardsvei 3, N-0372 Oslo, Norway..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
Copenhagen Univ Hosp, Rigshosp, Dept Pathol, Frederik Vs Vei 11, DK-2100 Copenhagen, Denmark..
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2016 (English)In: Pituitary, ISSN 1386-341X, E-ISSN 1573-7403, Vol. 19, no 4, 407-414 p.Article in journal (Refereed) PublishedText
Abstract [en]

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. 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. 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. 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.

Place, publisher, year, edition, pages
2016. Vol. 19, no 4, 407-414 p.
Keyword [en]
Pituitary adenoma, Isocitrate dehydrogenase, IDH1(R132H), Immunohistochemistry, Tissue microarrays
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-300440DOI: 10.1007/s11102-016-0720-7ISI: 000379350000009PubMedID: 27097804OAI: oai:DiVA.org:uu-300440DiVA: diva2:951529
Available from: 2016-08-09 Created: 2016-08-09 Last updated: 2016-08-09Bibliographically approved

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Casar-Borota, OliveraSundström, Magnus
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