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Int J Clin Exp Pathol 2010;3(3):226-237

Original Article
YKL-40 is directly produced by tumor cells and is inversely linked to EGFR in
glioblastomas

Department of Pathology, Division of Neuropathology, University of Kentucky, 800 Rose Street, Lexington, KY 40536, USA; Department of
Pathology, Division of Neuropathology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA

Received December 15, 2009; accepted December , 2009; available online January, 2009

Abstract: YKL-40 is a secreted chitinase-like molecule whose expression is associated with glioma grade. Expression is higher in
astrocytomas than oligodendrogliomas and has been reported to predict shorter survival and radiation resistance in glioblastomas (GBMs).  
Whether YKL-40 is directly produced by glioma cells or other admixed nonneoplastic cells, and whether it correlates with 1p/19q status or other
hallmark molecular abnormalities, are unclear.  A rank-order list of YKL-40 expression was determined immunohistochemically in 79 untreated
high-grade adult gliomas, including 28 anaplastic oligodendrogliomas (AOs) and 51 GBMs.  Relative YKL-40 expression was compared with
glioma class, key molecular alterations, and immunohistochemical markers via a series of Spearman rank correlations.  YKL-40 mRNA in situ
hybridization with colocalization assessment via confocal microscopy was also performed.  YKL-40 mRNA was abundant in glioma cells as
well as reactive astrocytes, but was low in admixed neurons and macrophages.  YKL-40 expression was higher in GBMs than AOs (P < 0.0001)
and among GBMs, YKL-40 expression was lower in tumors with either EGFR amplification (P = 0.005) or elevated EGFR expression (P =
0.001).  Among AOs, no difference in YKL-40 expression was seen in tumors with 1p19q codeletion (P = 0.3), but loss of heterozygosity in
10q23 correlated with increased YKL-40 expression (P = 0.03).  These data suggest that YKL-40 is predominantly expressed by neoplastic
glial cells and is related to certain key molecular alterations. (IJCEP912001).

Key words: YKL-40;glioblastoma, oligodendroglioma, EGFR; 1p19q; 10q

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