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  • Gold Nanoparticles as a Tool for Detecting Tumor Margins of Glioblastoma Multiforme

    Final Number:

    david hazon; Neelan Joseph Marianayagam MD, PhD; Orit Barinfeld MS; Shalom Michowiz MD; Susana Fichman-Horn; Asaf Olshinka MD; Ela Kaganovski MD; Avraham Hirshberg; Dror Fixler; Nitza Goldenberg-Cohen MD

    Study Design:
    Laboratory Investigation

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2016 Annual Meeting

    Introduction: Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Complete resection is nearly impossible. Overexpression of epithelial growth factor receptor (EGFR) has been associated with level of malignancy and with possible prognosis. In this study we use EGFR overexpression to mark tumor margins and infiltration to adjacent tissue, using anti-EGFR antibodies conjugated to gold nano-particles (GNPs). Immuno-staining is used in conjunction with molecular analysis of EGFR over-expression.

    Methods: Fourteen GBM samples were collected according to Institutional and National ethic committee's approval. DNA was extracted from fresh tumor samples and analyzed for EGFR overexpression using real time PCR. The gene expression status (polysomy or amplification of EGFR) was analyzed by calculating the ratio of expression between the following genes: EGFR, GPER and RNaseP. Immuno-staining with anti EGFR-GNP conjugated antibodies was carried out in parallel. Stained tumor cells were detected using hyperspectral imaging. These samples were compared with routine hematoxylin eosin (H&E) staining.

    Results: Ten of the 14 (71%) GBM samples had EGFR overexpression. Amplification was detected in 50%, polysomy in 50% and one sample showed both amplification and polysomy. Four samples showed normal EGFR expression (29%). Tumor borders determined by anti EGFR-GNP conjugated staining extended into tissue previously considered "healthy" by pathological analysis.

    Conclusions: The high level of expression of EGFR in GBM in the majority (71%) of the samples is in line with recent publications, and enables a new method to identify tumor borders, using anti EGFR antibodies conjugated to GNPs. We found a higher infiltration rate of tumor cells to the surrounding neural tissue. Staining with GNPs depends on the functional status of the tumor and may correlate with level of malignancy and prognosis. In the future this technology may enable in-vivo detection of the real tumor margins to facilitate complete resection of GBM.

    Patient Care: This research provides a possible tool for achieving complete resection of Glioblastoma multiforme and therefore has the potential to provide better outcomes for patients with the disease.

    Learning Objectives: At the conclusion of this session, participants should be able to: 1) Identify the importance of EGFR overexpression in prognosis of GBM, 2)Understand the different types of expression patterns of EGFR in GBM,3) Understand the importance of identifying the complete resection margins of GBM.


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