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Published in: Acta Neurochirurgica 8/2018

Open Access 01-08-2018 | Original Article - Tumor - Meningioma

SSTR-2 as a potential tumour-specific marker for fluorescence-guided meningioma surgery

Authors: B. M. Dijkstra, A. Motekallemi, W. F. A. den Dunnen, J. R. Jeltema, G. M. van Dam, F. A. E. Kruyt, R. J. M. Groen

Published in: Acta Neurochirurgica | Issue 8/2018

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Abstract

Background

Meningiomas are the most frequently occurring primary intracranial tumours in adults. Surgical removal can only be curative by complete resection; however surgical access can be challenging due to anatomical localization and local invasion of bone and soft tissues. Several intraoperative techniques have been tried to improve surgical resection, including intraoperative fluorescence guided imaging; however, no meningioma-specific (fluorescent) targeting has been developed yet. Here, we aimed to identify the most promising biomarkers for targeted intra-operative fluorescence guided meningioma surgery.

Methods

One hundred forty-eight meningioma specimens representing all meningioma grades were analysed using immunohistochemistry (IHC) on tissue microarrays (TMAs) to determine expression patterns of meningioma biomarkers epithelial membrane antigen (EMA), platelet-derived growth factor β (PDGF-β), vascular endothelial growth factor α (VEGF-α), and somatostatin receptor type 2 (SSTR-2). Subsequently, the most promising biomarker was selected based on TArget Selection Criteria (TASC). Marker expression was examined by IHC in 3D cell culture models generated from freshly resected tumour material.

Results

TMA-IHC showed strongest staining for SSTR-2. All cases were positive, with 51.4% strong/diffuse, 30.4% moderate/diffuse and only 18.2% focal/weak staining patterns. All tested biomarkers showed at least weak positivity in all meningiomas, regardless of WHO grade. TASC analysis showed that SSTR-2 was the most promising target for fluorescence guided imaging, with a total score of 21 (out of 22). SSTR-2 expression was determined on original patient tumours and 3D cultures of three established cultures.

Conclusions

SSTR-2 expression was highly sensitive and specific in all 148 meningiomas, regardless of WHO grade. According to TASC analysis, SSTR-2 is the most promising receptor for meningioma targeting. After establishing in vitro meningioma models, SSTR-2 cell membrane expression was confirmed in two of three meningioma cultures as well. This indicates that specific fluorescence in an experimental setting can be performed for the further development of targeted fluorescence guided meningioma surgery and near-infrared fluorescent tracers targeting SSTR-2.
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Metadata
Title
SSTR-2 as a potential tumour-specific marker for fluorescence-guided meningioma surgery
Authors
B. M. Dijkstra
A. Motekallemi
W. F. A. den Dunnen
J. R. Jeltema
G. M. van Dam
F. A. E. Kruyt
R. J. M. Groen
Publication date
01-08-2018
Publisher
Springer Vienna
Published in
Acta Neurochirurgica / Issue 8/2018
Print ISSN: 0001-6268
Electronic ISSN: 0942-0940
DOI
https://doi.org/10.1007/s00701-018-3575-z

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