Original contribution
GLUT-1 expression in mesenchymal tumors:
an immunohistochemical study of 247 soft
tissue and bone neoplasms
William A. Ahrens MD, Robert V. Ridenour III MD, Bolette L. Caron,
Dylan V. Miller MD, Andrew L. Folpe MD
⁎
Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, USA
Received 25 January 2008; revised 6 March 2008; accepted 10 March 2008
Keywords:
GLUT-1;
Perineurioma;
Hemangioma;
Hypoxia;
Sarcoma;
HIF1-α
Summary GLUT-1, an erythrocyte-type glucose transporter protein expressed in juvenile hemangiomas,
has recently been shown to be a sensitive marker of perineurial cells and their tumors in a small number
of cases. However, GLUT-1 expression has not been systematically examined in other mesenchymal
neoplasms. Prompted by a recent report of GLUT-1 expression in epithelioid sarcoma, a tumor not
generally felt to show perineurial differentiation, we examined GLUT-1 expression in a wide variety of
mesenchymal tumors. Sections from 247 mesenchymal tumors of a variety of histologic subtypes were
retrieved from our archives and immunostained for GLUT-1 using heat-induced epitope retrieval and the
DAKO ADVANCE detection system (DAKO, Carpinteria, CA). Scoring was as follows: negative (b5%
of cells), 1+ (5%-25% of cells), 2+ (25%-50% of cells), and 3+ (N50% of cells). All benign nerve sheath
tumors showed a peripheral rim of positive normal perineurial cells, with 2 neurofibromas and 3
schwannomas showing more extensive staining. Three of 4 perineuriomas showed strong GLUT-1
expression. All juvenile hemangiomas were GLUT-1 positive. GLUT-1 expression was also seen in a
wide variety of benign and malignant mesenchymal tumors. However, GLUT-1 expression was absent
in nonjuvenile hemangioma endothelial tumors and in almost all low-grade lesions that enter the
histologic differential diagnosis of perineurial tumors, including low-grade fibromyxoid sarcoma,
dermatofibrosarcoma protuberans, and myxofibrosarcoma. We conclude that GLUT-1 expression in
mesenchymal tumors is by no means specific for perineurial differentiation, but may instead represent
upregulation of this protein within hypoxic zones, secondary to upstream activation of proteins such as
hypoxia-inducible factor 1-α.
© 2008 Elsevier Inc. All rights reserved.
1. Introduction
GLUT-1 is an erythrocyte-type glucose transporter
protein and a member of the facilitative cell-surface glucose
transporter family which includes 5 other isoforms [1]. It was
originally purified from human erythrocyte membranes [2]
and has been subsequently identified in the brain capillary
endothelium, where it plays a critical role in the transport of
glucose across the blood-brain barrier [3]. In addition to its
role as a glucose transporter, GLUT-1 is also known to play
an important role in the cellular response to hypoxia, as a
downstream target of hypoxia-inducible factor 1-α (HIF1-α)
[4]. Constitutive GLUT-1 expression has been documented
⁎
Corresponding author.
E-mail address: folpe.andrew@mayo.edu (A. L. Folpe).
www.elsevier.com/locate/humpath
0046-8177/$ – see front matter © 2008 Elsevier Inc. All rights reserved.
doi:10.1016/j.humpath.2008.03.002
Human Pathology (2008) 39, 1519–1526