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

Abstract EN

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.