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Pathology Research International
Volume 2011 (2011), Article ID 216086, 19 pages
http://dx.doi.org/10.4061/2011/216086
Research Article

Morphological Analysis of CDC2 and Glycogen Synthase Kinase 3β Phosphorylation as Markers of G2 → M Transition in Glioma

Division of Neuropathology, Department of Pathology, University of California, San Francisco, 505 Parnassus Avenue, Moffit-Long Hospital, San Francisco, CA 94143, USA

Received 3 July 2010; Accepted 18 February 2011

Academic Editor: H. A. Lehr

Copyright © 2011 José Javier Otero and Tarik Tihan. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

G2 → M transition is a strategic target for glioma chemotherapy. Key players in G2 → M transition include CDC2 and glycogen synthase kinase 3β (GSK3β), which are highly regulated by posttranslational phosphorylation. This report is a morphological analysis of CDC2 and GSK3β phosphorylation using immunohistochemistry in gliomas with different biological properties. GBM showed a 2.8-fold and 5.6-fold increase in number of cells positive for pThr161CDC2 and a 4.2- and 6.9-fold increase in number of cells positive for pTyr15CDC2 relative to oligodendroglioma and ependymoma, respectively. Elevated labeling for inhibited phospho-CDC2 (pTyr15CDC) correlates with elevated levels of phosphorylated glycogen synthase kinase 3β (GSK3β). 71% of the GBM cases showed intermediate to high intensity staining for pSer9SGK3β 53% of oligodendroglioma, and 73% of ependymoma showed low intensity staining. CDC2 gene amplification correlates with increased survival in glioblastoma multiforme (GBM) and astrocytoma WHO grades II-III, but not in oligodendroglioma WHO grades II-III.