| 1. |
- Abdellah, Tebani, et al.
(författare)
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Annotation of pituitary neuroendocrine tumors with genome-wide expression analysis
- 2021
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Ingår i: Acta neuropathologica communications. - : BioMed Central (BMC). - 2051-5960. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Pituitary neuroendocrine tumors (PitNETs) are common, generally benign tumors with complex clinical characteristics related to hormone hypersecretion and/or growing sellar tumor mass. PitNETs can be classified based on the expression pattern of anterior pituitary hormones and three main transcriptions factors (TF), SF1, PIT1 and TPIT that regulate differentiation of adenohypophysial cells. Here, we have extended this classification based on the global transcriptomics landscape using tumor tissue from a well-defined cohort comprising 51 PitNETs of different clinical and histological types. The molecular profiles were compared with current classification schemes based on immunohistochemistry. Our results identified three main clusters of PitNETs that were aligned with the main pituitary TFs expression patterns. Our analyses enabled further identification of specific genes and expression patterns, including both known and unknown genes, that could distinguish the three different classes of PitNETs. We conclude that the current classification of PitNETs based on the expression of SF1, PIT1 and TPIT reflects three distinct subtypes of PitNETs with different underlying biology and partly independent from the expression of corresponding hormones. The transcriptomic analysis reveals several potentially targetable tumor-driving genes with previously unknown role in pituitary tumorigenesis.
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| 2. |
- Alfstad, K Å, et al.
(författare)
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Acute postoperative seizures after epilepsy surgery : a long-term outcome predictor?
- 2011
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 123:1, s. 48-53
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The prognostic value of acute postoperative seizures (APS) after epilepsy surgery is much debated. This study evaluated APS, defined as seizures in the first week post-surgery, as a predictor of long-term seizure outcome, and investigated the utility of other potential outcome predictors.MATERIALS AND METHODS: Medical records of 48 patients with temporal and extra-temporal epilepsy surgery were studied. Forty patients had lesional surgery. All had at least 2 year postoperative follow-up.RESULTS: At 2 year follow-up, 25 patients (53%) were seizure free. Univariate analysis showed that APS (P = 0.048), using ≥ six AEDs prior to surgery (P = 0.03), pathological postoperative EEG (P = 0.043) and female gender (P = 0.012) were associated with seizure recurrence.CONCLUSIONS: Univariate analysis indicate that APS, a high number of AEDs used prior to surgery, and pathological postoperative EEG are possible predictors of seizure recurrence after epilepsy surgery. Only gender retained significance in the multivariate analysis.
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| 3. |
- Asa, S L, et al.
(författare)
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From pituitary adenoma to pituitary neuroendocrine tumor (PitNET) : an International Pituitary Pathology Club proposal
- 2017
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Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 24:4, s. C5-C8
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Tidskriftsartikel (refereegranskat)abstract
- The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.
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| 4. |
- Asa, Sylvia L., et al.
(författare)
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Pituitary neuroendocrine tumors : a model for neuroendocrine tumor classification
- 2021
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Ingår i: Modern Pathology. - : Springer Nature. - 0893-3952 .- 1530-0285. ; 34:9, s. 1634-1650
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Forskningsöversikt (refereegranskat)abstract
- The classification of adenohypophysial neoplasms as "pituitary neuroendocrine tumors" (PitNETs) was proposed in 2017 to reflect their characteristics as epithelial neuroendocrine neoplasms with a spectrum of clinical behaviors ranging from small indolent lesions to large, locally invasive, unresectable tumors. Tumor growth and hormone hypersecretion cause significant morbidity and mortality in a subset of patients. The proposal was endorsed by a WHO working group that sought to provide a unified approach to neuroendocrine neoplasia in all body sites. We review the features that are characteristic of neuroendocrine cells, the epidemiology and prognosis of these tumors, as well as further refinements in terms used for other pituitary tumors to ensure consistency with the WHO framework. The intense study of PitNETs has provided information about the importance of cellular differentiation in tumor prognosis as a model for neuroendocrine tumors in different locations.
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| 5. |
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| 6. |
- Burman, Pia, et al.
(författare)
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Aggressive Pituitary Tumors and Pituitary Carcinomas : From Pathology to Treatment
- 2023
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 108:7, s. 1585-1601
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Forskningsöversikt (refereegranskat)abstract
- Aggressive pituitary tumors (APTs) and pituitary carcinomas (PCs) are heterogeneous with regard to clinical presentation, proliferative markers, clinical course, and response to therapy. Half of them show an aggressive course only many years after the first apparently benign presentation. APTs and PCs share several properties, but a Ki67 index greater than or equal to 10% and extensive p53 expression are more prevalent in PCs. Mutations in TP53 and ATRX are the most common genetic alterations; their detection might be of value for early identification of aggressiveness. Treatment requires a multimodal approach including surgery, radiotherapy, and drugs. Temozolomide is the recommended first-line chemotherapy, with response rates of about 40%. Immune checkpoint inhibitors have emerged as second-line treatment in PCs, with currently no evidence for a superior effect of dual therapy compared to monotherapy with PD-1 blockers. Bevacizumab has resulted in partial response (PR) in few patients; tyrosine kinase inhibitors and everolimus have generally not been useful. The effect of peptide receptor radionuclide therapy is limited as well. Management of APT/PC is challenging and should be discussed within an expert team with consideration of clinical and pathological findings, age, and general condition of the patient. Considering that APT/PCs are rare, new therapies should preferably be evaluated in shared standardized protocols. Prognostic and predictive markers to guide treatment decisions are needed and are the scope of ongoing research.
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| 7. |
- 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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| 8. |
- Casar-Borota, Olivera, et al.
(författare)
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A novel dynamin-2 gene mutation associated with a late-onset centronuclear myopathy with necklace fibres
- 2015
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Ingår i: Neuromuscular Disorders. - : Elsevier BV. - 0960-8966 .- 1873-2364. ; 25:4, s. 345-348
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Tidskriftsartikel (refereegranskat)abstract
- Nuclear centralisation and internalisation, sarcoplasmic radiating strands and type 1 muscle fibre predominance and hypotrophy characterise dynamin-2 (DNM2) associated centronuclear myopathy, whereas necklace fibres are typically seen in late onset myotubularin-1 (MTM1)-related myopathy. We report a woman with unilateral symptoms probably related to brachial plexus neuritis. Electromyography revealed localised neuropathic and generalised myopathic abnormalities. The typical features of DNM2 centronuclear myopathy with additional necklace fibres were found in the muscle biopsy. Sequencing of the DNM2 and MTM1 genes revealed a novel heterozygous missense mutation in exon 18 of the DNM2, leading to replacement of highly conserved proline at position 647 by arginine. The muscle symptoms have not progressed during the 3-year follow-up. However, the patient has developed bilateral subtle lens opacities. Our findings support the concept that necklace fibres may occasionally be found in DNM2-related myopathy, possibly indicating a common pathogenic mechanism in DNM2 and MTM1 associated centronuclear myopathy. (C) 2015 Elsevier B.V. All rights reserved.
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| 9. |
- Casar-Borota, Olivera, et al.
(författare)
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A novel dynamin-2 gene mutation associated with a late-onset centronuclear myopathy with unusual clinical presentation and necklace fibres
- 2012
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Ingår i: Neuromuscular Disorders. - Oxford : Elsevier BV. - 0960-8966 .- 1873-2364. ; 22:9-10, s. 843-843
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Nuclear centralisation and internalisation, sarcoplasmic radiating strands and type 1 muscle fibre predominance and hypotrophy are morphologic features of centronuclear myopathy (CNM) related to dynamin-2 (DNM2) gene defects, whereas necklace fibres characterise late-onset myopathy associated with myotubularin-1 (MTM1) gene defects. We report a 40-year-old woman with 1-year history of pain and paresthesia in the left shoulder and arm that was clinically interpreted as brachial plexus neuritis. Electromyography revealed both myopathic and neuropathic abnormalities, and because of the myopathic changes a muscle biopsy was performed. The typical morphologic features of dynamin-2 CNM with additional numerous necklace fibres were found in the muscle biopsy. Sequencing of the DNM2 and MTM1 genes revealed a not previously described heterozygous missense mutation in exon 18 of DNM2 leading to replacement of highly conserved Proline in position 647 by Arginine. The muscle symptoms have not progressed during the two-year follow-up, but the patient has developed bilateral subtle lens opacities. Necklace fibres were originally described as fibres that had usually a small diameter and internalized nuclei aligned in a basophilic ring at a few micrometers beneath the sarcolemma. They were described in association with myopathies caused by MTM1 mutations, and similar but not identical fibres have also been reported in a case of DNM2 associated CNM. Our findings support the concept that necklace fibres are not specific but indicate common pathogenic mechanisms in DNM2 and MTM1 associated CNM. This case report expands the clinical, morphological and molecular genetic variability of DNM2 associated CNM.
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