Synaptic Vesicle Protein 2 and Vesicular Monoamine Transporter 1 and 2 Are Expressed in Neuroblastoma

Kleopatra Georgantzi,Apostolos V Tsolakis,Rolf Christofferson,Åke Jakobson,Eva Tiensuu Janson,Lars Grimelius

doi:10.1007/s12022-019-09584-3

Kleopatra Georgantzi, Apostolos V Tsolakis + Show 4 more

Open Access

https://doi.org/10.1007/s12022-019-09584-3

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Abstract

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.

Highlights

Neuroblastoma (NB) is the most common extracranial tumor in children, originating from cells of the adrenal medulla or the sympathetic nervous system
The aims of this study were to investigate the immunohistochemical expression of the general NE markers Chromogranin A (CgA), syn, synaptic vesicle protein 2 (SV2) and the more specific markers monoamine transporters vesicular monoamine transporter 1 (VMAT1) and VMAT2 in NB, and to evaluate these markers’ usefulness in the histopathological diagnostics
Six tumors had 90% or more immunoreactive cells for VMAT2 while no tumor showed such a high IR for VMAT1 (Table 2)

Summary

Introduction

Neuroblastoma (NB) is the most common extracranial tumor in children, originating from cells of the adrenal medulla or the sympathetic nervous system. A NE phenotype can be assessed by the expression of general and specific NE markers. Chromogranin A (CgA), a general NE marker, and the more specific markers vesicular monoamine transporter 1 and 2 (VMAT1 and VMAT2) are associated with large dense core vesicles. CgA and syn are cornerstones in the histopathological diagnostics of neuroendocrine tumors (NETs) including NB [6]. Another broad spectrum NE marker, INSM1, has been used frequently in the past 4 years for the workup of NETs [7]. This biomarker has been reported to stain NB [8]

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