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. 2011 Apr;33(4):808-16.
doi: 10.1002/jmri.22517.

Choline metabolism, proliferation, and angiogenesis in nonenhancing grades 2 and 3 astrocytoma

Tracy R McKnight  1 , Kenneth J Smith, Philip W Chu, King S Chiu, Colleen P Cloyd, Susan M Chang, Joanna J Phillips, Mitchel S Berger
Affiliations

Choline metabolism, proliferation, and angiogenesis in nonenhancing grades 2 and 3 astrocytoma

Tracy R McKnight et al. J Magn Reson Imaging. 2011 Apr.

Abstract

Purpose: To study choline metabolism in biopsies from nonenhancing Grade 2 (AS2) and Grade 3 (AS3) astrocytomas to determine whether (1) phosphocholine (PC) dominates in AS3, and (2) PC is associated with proliferation or angiogenesis. PC and glycerophosphocholine (GPC) are involved in phospholipid metabolism that accompanies mitosis. PC is the predominant peak in Grade 4 astrocytoma (GBM) while GPC dominates in AS2.

Materials and methods: We used high resolution magic angle spinning magnetic resonance spectroscopy to compare the concentrations of 10 metabolites in 41 biopsies (16 AS2 and 25 AS3) from 24 tumors. Immunohistochemistry was performed on paired biopsies to determine the cell density, Ki-67 proliferation index, and vascular endothelial growth factor (VEGF) angiogenic marker expression.

Results: AS3 had higher PC than AS2; however, the PC:GPC was less than 1 in all cases irrespective of tumor grade. Within tumors, GPC increased with Ki-67 and PC and tCho increased with cell density. There was no association between any choline compound and VEGF.

Conclusion: These data suggest that PC:GPC less than 1 is not unique to low grade glioma. Furthermore, the PC concentration that is a marker of aggressive glial tumors is not tightly linked to cell proliferation or angiogenesis in nonenhancing astrocytomas.

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Figures

Figure 1
Figure 1
Non-enhancing Grade 3 astrocytoma (A) contrast-enhanced T1-weighted MRI showing PRESS box (black) where MRS data was acquired and biopsy location (red). (B) 3D-MR spectra and (C) apparent diffusion coefficient image map were that were used to select the biopsy location prior to surgery. Post-surgical (F) HRMAS MR spectrum, immunohistochemical (D) Ki-67 and (E) VEGF labeling of biopsied tissue sample.
Figure 2
Figure 2
Distribution of VEGF immunopositive tissue samples among non-enhancing Grades 2 (AS2) and Grades 3 (AS3) glioma. None of the Grade 2 samples expressed VEGF while approximately half (56%) of the Grade 3 samples were VEGF positive.
Figure 3
Figure 3
Example 1D and 2D TOCSY spectra from (A) AS2 and (B) AS3 showing GPC as the dominant choline compound.
Figure 4
Figure 4
Ratio of choline compounds to total choline in non-enhancing Grades 2 and 3 astrocytoma. There was no significant difference in any of the ratios. The GPC/tCho ratio was the highest in all samples. GPC = glycerophosphocholine, PC = phosphocholine, fCho = free Choline
Figure 5
Figure 5
Associations between choline compounds and Ki-67 proliferation index in non-enhancing astrocytoma. Spearman rank correlation showed that tCho (r = 0.432, p = 0.005), fCho (r = 0.332, p = 0.034) and GPC (r = 0.397, p = 0.015) were correlated with proliferation while PC (r = 0.286, p = 0.070) had a similar trend but did not reach statistical significance.
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References

    1. CBTRUS . 2009-2010 CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in Eighteen States in 2002-2006. Hinsdale, IL: Central Brain Tumor Registry of the United States; 2009.
    1. Kleihues P, Burger PC, Scheithauer BW, Zülch KJ. Histological typing of tumours of the central nervous system. Berlin ; New York: Springer-Verlag; 1993. p. 112.
    1. Erb G, Elbayed K, Piotto M, et al. Toward improved grading of malignancy in oligodendrogliomas using metabolomics. Magn Reson Med. 2008;59(5):959–965. - PubMed
    1. Opstad KS, Bell BA, Griffiths JR, Howe FA. Taurine: a potential marker of apoptosis in gliomas. Br J Cancer. 2009;100(5):789–794. - PMC - PubMed
    1. Righi V, Roda JM, Paz J, et al. 1H HR-MAS and genomic analysis of human tumor biopsies discriminate between high and low grade astrocytomas. NMR Biomed. 2009;22(6):629–637. - PubMed

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