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GLUT1 protein expression correlates with unfavourable histologic category and high risk in patients with neuroblastic tumours

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Abstract

GLUT1 is a hypoxia-induced gene that has many biologically important functions, and the overexpression of the GLUT1 protein correlates with poor prognosis in several adult cancers. The clinical significance of the GLUT1 protein in peripheral neuroblastic tumours (NTs) has not been comprehensively documented. In the present retrospective study, immunohistochemical analyses revealed the presence of GLUT1 in 44/96 (46 %) NTs. Membranous GLUT1 was present in neuroblasts of 44/87 neuroblastomas (NBs) and nodular ganglioneuroblastomas (nGNBs) but was absent in ganglion cells. The presence of GLUT1 was significantly increased in NBs and nGNBs compared with maturing ganglioneuromas and intermixed ganglioneuroblastomas (P < 0.001). The proportion of NBs and nGNBs expressing GLUT1 was significantly increased in the high-risk and low/intermediate-risk groups compared with the very-low-risk group (P = 0.022) and the unfavourable compared with the favourable pathology prognostic group (P = 0.027). In the Cox regression analyses, GLUT1 expression indicated a worse overall survival (OS; hazard rate ratio (HR) 2.29, P = 0.053) and event-free survival (EFS; HR 1.68, P = 0.181) which was not attenuated by adjustment for the mitosis–karyorrhexis index and MYCN amplification (OS: adjusted HR 2.44, P = 0.053 and EFS: adjusted HR 1.63, P = 0.244). This indicated that GLUT1 protein expression was independent of mitosis–karyorrhexis index and MYCN amplification as a prognostic factor. Our data may have clinical significance because GLUT1 was also present in a higher proportion of high-risk NTs.

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Abbreviations

GLUT1:

Glucose transporter protein 1

GLUT1 :

Glucose transporter 1 gene

SLC2A1 :

Solute carrier family 2A (facilitative glucose transporter) member 1

HIF1A :

Hypoxia-inducible factor-1α gene

HIF2A :

Hypoxia-inducible factor-2α gene

HIF-1α:

Hypoxia-inducible factor-1α protein

HIF-2α:

Hypoxia-inducible factor-2α protein

NT:

Neuroblastic tumour

NB:

Neuroblastoma

GNB:

Ganglioneuroblastoma

iGNB:

Intermixed ganglioneuroblastoma

nGNB:

Nodular ganglioneuroblastoma

GN:

Ganglioneuroma

MKI:

Mitosis–karyorrhexis index

INPC:

International Neuroblastoma Pathology Classification

INRG:

International Neuroblastoma Risk Group

INSS:

International Neuroblastoma Staging System

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Acknowledgments

The authors would like to thank Above and Beyond Charities of the University Hospitals Bristol Foundation Trust and Ince and Company for their financial support. The authors would like to thank Mike Luckett and Michelle Somerville for the technical support. The authors are grateful to the clinicians, radiologists and all the individuals who were involved in the management of the patients.

Conflict of interest

The authors declare that there is no conflict of interest. No part of the article has been published or submitted elsewhere, and there are no financial relationships that may lead to conflict of interest. The manuscript has been read and approved by all authors.

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Authors and Affiliations

  1. Department of Histopathology, Bristol Royal Infirmary, Bristol, BS2 8HW, UK

    Pramila Ramani & Alison Headford

  2. School of Cellular and Molecular Medicine, Faculty of Medical and Veterinary Sciences, University of Bristol, University Walk, Bristol, BS8 1TD, UK

    Pramila Ramani

  3. School of Social and Community Medicine, University of Bristol, Canynge Hall, 39 Whatley Road, Bristol, BS8 2PS, UK

    Margaret T May

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  1. Pramila Ramani
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Correspondence to Pramila Ramani.

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Ramani, P., Headford, A. & May, M.T. GLUT1 protein expression correlates with unfavourable histologic category and high risk in patients with neuroblastic tumours. Virchows Arch 462, 203–209 (2013). https://doi.org/10.1007/s00428-012-1370-4

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  • DOI: https://doi.org/10.1007/s00428-012-1370-4

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