Abstract
Overactivation of epidermal growth factor receptor (EGFR) signaling has been recognized as an important step in the pathogenesis and progression of multiple forms of cancer of epithelial origin. Reports regarding EGFR family members in brain tumors are sparse and, thus, the significance of EGFR expression in childhood brain tumors is unclear. In this study, the expression of the EGFR family members was analyzed in 22 medulloblastomas. During the immunohistochemical study, a sensitive, four-step, alkaline phosphatase conjugated antigen detection technique was employed. The results demonstrated the presence of c-erbB-2 (HER-2) and c-erbB-4 (HER-4) in 10 to 50% of the neoplastic cells of high-grade glial tumors with high immunoreactivity, while c-erbB-3 (HER-3) was only detected in less than 10% of the neoplastically-transformed cells. In a follow-up, 70% of children, usually under 4 years of age, with c-erbB-2 (HER-2)-positive MEDs/PNETs, succumbed to the cancer. The Kaplan-Meier estimation revealed a significant correlation between c-erbB-2 expression and survival (p=0.002), suggesting that c-erbB-2 (HER-2) is probably a prognostic marker for limited survival. Medulloblastoma is the most common malignant brain tumor that occurs during childhood. Multimodality treatment regimens have substantially improved survival in this disease; however, the tumor is incurable in about one-third of patients with medulloblastoma, and the current treatment has a detrimental effect on long-term survivors. As such, the results of this study further support the idea that targeting EGFR alone, or in combination with its downstream mediators, represents a promising new approach for the management of childhood brain tumors. Moreover, c-erbB-2 (HER-2) expression may also be of use in better classifying brain tumors. “The growth and proliferation of cells are usually tightly regulated processes that are activated by stimuli from their environment. Epidermal growth factor (EGF)-related peptides represent a class of molecules that can trigger cell proliferation, among several cellular processes, such as differentiation, migration, and survival. Binding of EGF-like peptides to the EGF receptor (EGFR) at the cell surface leads to a cascade of intracellular reactions that transduce signals to the nucleus, resulting in particular gene expression patterns. However, in many tumor cells, the regulation of EGFR activity is lost, due to increased or aberrant expression of the receptor or its ligands, and this contributes to many processes important for tumor growth, including cell proliferation, survival, angiogenesis, invasion, and metastasis.”
- Epidermal growth factor (EGF)
- epidermal growth factor receptor (EGFR) or c-erbB-1 (HER-1)
- c-erbB-2 (HER-2)
- c-erbB-3 (HER-3)
- c-erbB-4 (HER-4)
- medulloblastoma (MED)
- immunohistochemistry
Footnotes
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Abbreviations: AA, anaplastic astrocytoma; GBM, glioblastoma multiforme; MoAB, monoclonal antibody; IP, immuno-phenotype.
- Received March 21, 2005.
- Accepted June 9, 2005.
- Copyright © 2005 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved