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- Casar-Borota, Olivera, et al.
(författare)
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A high-throughput analysis of the IDH1(R132H) protein expression in pituitary adenomas
- 2016
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 19:4, s. 407-414
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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- Kolnes, Anders Jensen, et al.
(författare)
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TGFBR3L is associated with gonadotropin production in non-functioning gonadotroph pituitary neuroendocrine tumours
- 2023
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Ingår i: Pituitary. - : Springer. - 1386-341X .- 1573-7403. ; 26:2, s. 227-236
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Transforming growth factor-beta receptor 3-like (TGFBR3L) is a pituitary enriched membrane protein selectively detected in gonadotroph cells. TGFBR3L is named after transforming growth factor-beta receptor 3 (TGFBR3), an inhibin A co-receptor in mice, due to sequence identity to the C-terminal region. We aimed to characterize TGFBR3L detection in a well-characterized, prospectively collected cohort of non-functioning pituitary neuroendocrine tumours (NF-PitNETs) and correlate it to clinical data.Methods 144 patients operated for clinically NF-PitNETs were included. Clinical, radiological and biochemical data were recorded. Immunohistochemical (IHC) staining for FSH beta and LH beta was scored using the immunoreactive score (IRS), TGFBR3L and TGFBR3 were scored by the percentage of positive stained cells.Results TGFBR3L staining was selectively present in 52% of gonadotroph tumours. TGFBR3L was associated to IRS of LH beta (median 2 [IQR 0-3] in TGFBR3L negative and median 6 [IQR 3-9] in TGFBR3L positive tumours, p < 0.001), but not to the IRS of FSH beta (p = 0.32). The presence of TGFBR3L was negatively associated with plasma gonadotropin concentrations in males (P-FSH median 5.5 IU/L [IQR 2.9-9.6] and median 3.0 [IQR 1.8-5.6] in TGFBR3L negative and positive tumours respectively, p = 0.008) and P-LH (median 2.8 IU/L [IQR 1.9-3.7] and median 1.8 [IQR 1.1-3.0] in TGFBR3L negative and positive tumours respectively, p = 0.03). TGFBR3 stained positive in 22% (n = 25) of gonadotroph tumours with no correlation to TGFBR3L.Conclusion TGFBR3L was selectively detected in half (52%) of gonadotroph NF-PitNETs. The association to LH beta staining and plasma gonadotropins suggests that TGFBR3L may be involved in hormone production in gonadotroph NF-PitNETs.
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- Manojlovic-Gacic, Emilija, et al.
(författare)
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Histopathological classification of non-functioning pituitary neuroendocrine tumors
- 2018
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 21:2, s. 119-129
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Forskningsöversikt (refereegranskat)abstract
- Non-functioning pituitary neuroendocrine tumors do not cause endocrine symptoms related to hypersecretion of adenohypophyseal hormones and are clinically characterized by symptoms due to growing sellar tumor mass. Histopathological classification of this tumor group has always been challenging due to their heterogeneity, limited knowledge on their biology, and diverse methodological problems. We have searched PubMed database for data related to the histopathological classification of non-functioning pituitary tumors and methods for its application. Principles of the classification and grading presented in the recently released 4th edition of the World Health Organization classification of endocrine tumors have been summarized. Based on the expression of anterior pituitary hormones and pituitary specific transcription factors, gonadotroph tumors dominate within the group of clinically non-functioning tumors, followed by corticotroph type; however, other less common types of the non-functioning tumors can be identified. Assessment of tumor cell proliferation is important to identify "high-risk adenomas." A few subtypes of non-functioning tumors belong to the category of potentially aggressive tumors, independent of the cell proliferation rate. Here, we present up to date criteria for the classification of clinically non-functioning pituitary tumors, offer a diagnostic approach for the routine clinical use, and emphasize a need for inclusion of prognostic and predictive markers in the classification.
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