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Synaptic Vesicle Protein 2 and Vesicular Monoamine Transporter 1 and 2 Are Expressed in Neuroblastoma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.ORCID iD: 0000-0001-9304-6144
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology. Karolinska Inst, Dept Oncol & Pathol, Stockholm, Sweden;Karolinska Univ Hosp Solna, CCK, Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Neuropediatrics/Paediatric oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Pediatric Surgery.
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2019 (English)In: Endocrine pathology, ISSN 1046-3976, E-ISSN 1559-0097, Vol. 30, no 3, p. 173-179Article in journal (Refereed) Published
Abstract [en]

Neuroblastoma (NB), the most common extracranial cancer in childhood, exhibits neuroendocrine (NE) differentiation. Two well-established NE markers, chromogranin A (CgA) and synaptophysin (syn), are used in the histopathological diagnostics. Our aims were to explore if the NE markers synaptic vesicle protein 2 (SV2) and vesicular monoamine transporter 1 (VMAT1) and 2 (VMAT2) also are expressed in human NB and if so, evaluate their usefulness in NB histopathological diagnostics. Tumor specimens from 21 NB patients, before and/or after chemotherapy, were immunostained for CgA, syn, SV2, VMAT1, and VMAT2. Clinical data was extracted from patients' records. SV2 was highly expressed in NB, as was CgA while syn was less frequently expressed compared to the other two. Both VMATs were expressed in several NB, VMAT2 in more cases than VMAT1 and its expression was similar to syn. Chemotherapy did not affect the immunoreactivity in an obvious way. SV2 was highly expressed in NB and can thus be useful marker in NB diagnostics. VMAT1 and VMAT2 were also expressed in NB but similar to syn less reliable as tumor markers.

Place, publisher, year, edition, pages
2019. Vol. 30, no 3, p. 173-179
Keywords [en]
neuroblastoma, neuroendocrine, immunohistochemistry, urine-dopamine, urine-HVA, urine-VMA, markers
National Category
Surgery Pediatrics Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-364674DOI: 10.1007/s12022-019-09584-3ISI: 000481425400001PubMedID: 31317476OAI: oai:DiVA.org:uu-364674DiVA, id: diva2:1259840
Available from: 2018-10-31 Created: 2018-10-31 Last updated: 2019-09-25Bibliographically approved
In thesis
1. On the Diagnostics of Neuroblastoma: Clinical and Experimental Studies
Open this publication in new window or tab >>On the Diagnostics of Neuroblastoma: Clinical and Experimental Studies
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Neuroblastoma (NB) is one of the most common childhood cancers. Patients with low stage tumor have high survival rate, while those with advanced stage and/or unfavorable molecular biology have poor prognosis. A correct histopathological diagnosis, clinical stage, and identified genetic aberrations are crucial for treatment stratification according to current protocol. The tumor sample is obtained either by fine needle aspiration, cutting needle biopsy or open biopsy. NB exhibits neuroendocrine differentiation by showing immunoreactivity for chromogranin A (CgA), synaptophysin (syn), and neuron specific enolase (NSE) and 90% of the patients have increased levels of urine catecholamine metabolites.

Experimental and clinical NB tumor samples were immunostained for somatostatin receptors (SSTRs) 1-5, somatostatin and CgA. Clinical tumor samples were also immunostained for syn, synaptic vesicle protein 2 (SV2), and vesicle monoamine transporter 1 (VMAT1) and 2 (VMAT 2). Blood samples from 92 patients were analyzed for level of CgA, NSE, and chromogranin B and compared with control groups. The urinary excretion of catecholamine metabolites was analyzed in samples collected at diagnosis. Clinical and laboratory data were extracted from patient records, including information on the diagnostic accuracy of ultrasound guided cutting needle biopsies (UCNB) and potential complications.

We found that NB expressed the different SSTRs and that receptor 2 was the most frequently expressed before chemotherapy. Furthermore, NB tumors showed immunoreactivity for SV2, VMAT 1 and VMAT2 alongside CgA and syn. The immunoreactivity of SV2 was comparable to CgA and superior to syn. Patients with NB had higher blood concentrations of CgA and NSE compared with controls. Patients with advanced stage disease, MYCN amplification and 1 p deletion had higher concentrations of both CgA and NSE while only NSE was correlated to outcome with higher concentrations in the deceased patients.

A high urinary excretion of homovanillic acid and dopamine were correlated to inferior outcome. UCNB were found to be safe and may provide all necessary diagnostic requirements for adequate therapy stratification according to current treatment protocols.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. p. 50
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1514
Keywords
Neuroendocrine, Immunohistochemistry, Urinary Catecholamine Metabolites, Markers, Outcome
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-364682 (URN)978-91-513-0499-1 (ISBN)
Public defence
2018-12-20, Rosénsalen, Akademiska barnsjukhuset, ingång 95/96, nbv, Uppsala, 13:15 (Swedish)
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Available from: 2018-11-29 Created: 2018-10-31 Last updated: 2018-12-27

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Georgantzi, KleopatraTsolakis, Apostolos V.Jakobson, ÅkeChristofferson, RolfTiensuu Janson, EvaGrimelius, Lars

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