PMID- 17146292 OWN - NLM STAT- MEDLINE DCOM- 20070116 LR - 20181201 IS - 0022-3069 (Print) IS - 0022-3069 (Linking) VI - 65 IP - 12 DP - 2006 Dec TI - Activation of STAT3, MAPK, and AKT in malignant astrocytic gliomas: correlation with EGFR status, tumor grade, and survival. PG - 1181-8 AB - 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. FAU - Mizoguchi, Masahiro AU - Mizoguchi M AD - Molecular Pathology Unit and Molecular Neuro-Oncology Laboratory, Department of Pathology, Cancer Center and Neurosurgical Service, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA. FAU - Betensky, Rebecca A AU - Betensky RA FAU - Batchelor, Tracy T AU - Batchelor TT FAU - Bernay, Derek C AU - Bernay DC FAU - Louis, David N AU - Louis DN FAU - Nutt, Catherine L AU - Nutt CL LA - eng GR - CA 57683/CA/NCI NIH HHS/United States GR - CA 95616/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - England TA - J Neuropathol Exp Neurol JT - Journal of neuropathology and experimental neurology JID - 2985192R RN - 0 (Biomarkers, Tumor) RN - 0 (STAT3 Transcription Factor) RN - 0 (STAT3 protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Astrocytoma/diagnosis/*enzymology/epidemiology MH - Biomarkers, Tumor/analysis/metabolism MH - Brain Neoplasms/diagnosis/*enzymology/epidemiology MH - Diagnosis, Differential MH - Disease Progression MH - Enzyme Activation/genetics MH - ErbB Receptors/*biosynthesis/genetics MH - Genetic Predisposition to Disease/genetics MH - Glioblastoma/diagnosis/*enzymology/epidemiology MH - Humans MH - Immunohistochemistry MH - Mitogen-Activated Protein Kinases/analysis/*metabolism MH - Mutation/genetics MH - Predictive Value of Tests MH - Prognosis MH - Proto-Oncogene Proteins c-akt/analysis/*metabolism MH - STAT3 Transcription Factor/analysis/*metabolism MH - Signal Transduction/physiology MH - Survival Rate/trends MH - Transcriptional Activation/genetics EDAT- 2006/12/06 09:00 MHDA- 2007/01/17 09:00 CRDT- 2006/12/06 09:00 PHST- 2006/12/06 09:00 [pubmed] PHST- 2007/01/17 09:00 [medline] PHST- 2006/12/06 09:00 [entrez] AID - 00005072-200612000-00010 [pii] AID - 10.1097/01.jnen.0000248549.14962.b2 [doi] PST - ppublish SO - J Neuropathol Exp Neurol. 2006 Dec;65(12):1181-8. doi: 10.1097/01.jnen.0000248549.14962.b2.