title: Role of Her-2/neu overexpression and clinical determinants of early mortality in glioblastoma multiforme.
abstract: Her-2/neu or c-erbB-2, a 185-kD protein is an important prognostic indicator/target for therapy in metastatic breast carcinoma. Recent reports have also identified a role for Her-2/neu overexpression in other solid tumors. We performed a retrospective analysis to evaluate the prevalence and prognostic role of Her-2/neu overexpression in patients with glioblastoma multiforme (GBM). Data collection (chart review) included demographic information, symptoms at presentation, histologic grade, survival time, and treatment offered. Testing for Her-2/neu overexpression was performed on paraffin-embedded archival tumor tissue using immunohistochemistry (IHC) (Hercep test). An IHC score of 2+ or greater was considered overexpression. An experienced pathologist who was blinded from the clinical history performed all the IHC testing. Between 1990 and 2001, 149 subjects (68 females, 81 males) with a biopsy-proven diagnosis of GBM were identified. Age range was 26 to 79 years (mean: 64 years) and overall mean survival was 12 months. Her-2/neu overexpression was detected in 23 patients (15.4%). Interestingly, the median survival for patients whose pathologic specimens revealed Her-2/neu overexpression was 4 months compared to those who lacked overexpression, in whom survival was 8 months. After adjusting for age, performance status, smoking history, and treatment, logistic regression analysis (with a survival of <3 months as the dependent variable) revealed that Her-2/neu overexpression significantly (p < 0.01) increased the odds of early mortality (<3 months). The results of our large study indicate that Her-2/neu overexpression may be a poor prognostic marker in patients with GBM. In addition, in a proportion of subjects (15.4%), Her-2/neu may be a potential target for tumor-specific monoclonal antibody therapy. The role of trastuzumab (alone or in combination with conventional therapy) needs to be evaluated.
authors.affiliation: Department of Internal Medicine, University of North Dakota School of Medicine and Health Sciences, Fargo, ND 58102, USA.
authors.forename: Vijay
authors.initials: V
authors.lastname: Koka
authors.forename: Anil
authors.initials: A
authors.lastname: Potti
authors.forename: Scott E
authors.initials: SE
authors.lastname: Forseen
authors.forename: Hassan
authors.initials: H
authors.lastname: Pervez
authors.forename: Genise N
authors.initials: GN
authors.lastname: Fraiman
authors.forename: Michael
authors.initials: M
authors.lastname: Koch
authors.forename: Ralph
authors.initials: R
authors.lastname: Levitt
mesh_terms: D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases