Activation of STAT3, MAPK, and AKT in malignant astrocytic gliomas: Correlation with EGFR status, tumor grade, and survival

Masahiro Mizoguchi, Rebecca Betensky, Tracy T. Batchelor, Derek C. Bernay, David N. Louis, Catherine L. Nutt

Research output: Contribution to journalArticle

Abstract

Diffuse astrocytic gliomas are the most common human glial tumors with glioblastoma being the most malignant form. Epidermal growth factor receptor (EGFR) gene amplification is one of the most common genetic changes in glioblastoma and can lead to the activation of various downstream signaling molecules, including STAT3, MAPK, and AKT. In this study, we investigated the activation status of these 3 signaling molecules as well as wild-type (EGFRwt) and mutant (EGFRvIII) EGFR in 82 malignant astrocytic gliomas (55 glioblastomas and 27 anaplastic astrocytomas) using immunohistochemistry. The presence of EGFRwt, but not EGFRvIII, immunopositivity correlated significantly with prevalent EGFR gene amplification in glioblastomas. STAT3 and AKT activation correlated significantly with EGFR status, although the correlation for p-STAT3 was attributed exclusively to EGFRvIII. The distribution of these 3 activated molecules varied significantly with tumor grade; although activation of STAT3 was essentially identical between anaplastic astrocytomas and glioblastomas, an increase in the activation of MAPK and AKT appeared to correlate with the progression of anaplastic astrocytoma to glioblastoma. Finally, activated STAT3 and AKT were marginally predictive of improved and worse prognosis, respectively. Taken together, these findings begin to elucidate the interrelationship between these signaling pathways in astrocytic gliomas in vivo.

Original languageEnglish (US)
Pages (from-to)1181-1188
Number of pages8
JournalJournal of Neuropathology and Experimental Neurology
Volume65
Issue number12
DOIs
StatePublished - Dec 1 2006

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Astrocytoma
Glioblastoma
Epidermal Growth Factor Receptor
Survival
Neoplasms
erbB-1 Genes
Gene Amplification
Neuroglia
Immunohistochemistry

Keywords

  • AKT
  • EGFR
  • Glioma
  • MAPK
  • Phosphorylation
  • STAT3

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Activation of STAT3, MAPK, and AKT in malignant astrocytic gliomas : Correlation with EGFR status, tumor grade, and survival. / Mizoguchi, Masahiro; Betensky, Rebecca; Batchelor, Tracy T.; Bernay, Derek C.; Louis, David N.; Nutt, Catherine L.

In: Journal of Neuropathology and Experimental Neurology, Vol. 65, No. 12, 01.12.2006, p. 1181-1188.

Research output: Contribution to journalArticle

Mizoguchi, Masahiro ; Betensky, Rebecca ; Batchelor, Tracy T. ; Bernay, Derek C. ; Louis, David N. ; Nutt, Catherine L. / Activation of STAT3, MAPK, and AKT in malignant astrocytic gliomas : Correlation with EGFR status, tumor grade, and survival. In: Journal of Neuropathology and Experimental Neurology. 2006 ; Vol. 65, No. 12. pp. 1181-1188.
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