title: Epidermal growth factor receptor (EGFR) expression in childhood brain tumors.
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.
authors.affiliation: Department of Pathology, University of Southern California, Keck School of Medicine, Los Angeles, CA, USA. Bodey18@aol.com
authors.forename: Bela
authors.initials: B
authors.lastname: Bodey
authors.forename: Hans E
authors.initials: HE
authors.lastname: Kaiser
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Siegel
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000941:Antigens / Q000096:biosynthesis; D001254:Astrocytoma / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism*; D002675:Child, Preschool; D066246:ErbB Receptors / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008527:Medulloblastoma / Q000378:metabolism / Q000628:therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D020893:Receptor, ErbB-3 / Q000096:biosynthesis; D066247:Receptor, ErbB-4
chemical_list: D000469:Alkaline Phosphatase; D000911:Antibodies, Monoclonal; D000941:Antigens; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C587689:ERBB4 protein, human