title: Determination of HER-2/neu overexpression and clinical predictors of survival in a cohort of 347 patients with primary malignant brain tumors.
abstract: BACKGROUND
  HER-2/neu overexpression has been associated with poor prognosis in a variety of malignancies. The extent and relevance of HER-2/neu overexpression in human central nervous system (CNS) malignancies is unclear. We retrospectively analyzed a large cohort of patients with primary malignant brain tumors to evaluate the role of HER-2/neu overexpression, clinical characteristics at presentation, and other predisposing factors as predictors of survival.
  
  
  METHODS
  Records of 347 adult patients (193 males, 154 females) diagnosed and followed between 1986 and 2001 with a biopsy-proven diagnosis of a primary malignant brain tumor at a tertiary care oncology center were reviewed. Archival pathologic samples were analyzed for HER-2/neu overexpression using the Hercep immunohistochemical (IHC) assay (DAKO). A score of 2+ or greater on the assay was considered positive for HER-2/neu overexpression. Mortality and its predictors were evaluated using multiple logistic regression. (This study was approved and reviewed by the Institutional Review Board Committee [IRB] of University of North Dakota School of Medicine and Health Sciences.)
  
  
  RESULTS
  Among the 347 adult patients with a mean age of 53 years (range; 41-73 years), overall mean survival was 23 months (range; 0-151 months). It was found that 10.4% of the archival pathologic samples showed presence of HER-2/neu overexpression by IHC. The HER-2/neu overexpression predicted significantly increased mortality [p = 0.01, analysis of variance (ANOVA)]. Other clinical predictors associated with increased mortality included site of tumor (occipital and parietal lobes) (p = 0.02, ANOVA), tumor histology (glioblastoma) (p < 0.01, ANOVA), and presenting symptom (nausea/vomiting) (p < 0.01, ANOVA). Also, there was a higher incidence of associated primary malignancies (outside the CNS) in the HER-2/neu overexpression group (30% vs. 7%).
  
  
  CONCLUSIONS
  HER-2/neu overexpression seen in 10.4% appears to predict a slight increased mortality in patients with primary malignant brain tumors, especially glioblastoma multiforme, and is associated with a high incidence of a second primary malignancy outside the CNS. Additionally, our data suggests that other clinical variables were predictive of increased mortality, including tumor location (occipital), histology (glioblastoma), and presenting symptoms (nausea/vomiting). The large, heterogeneous sample employed in our study allows more definitive conclusions to be made with regard to the usefulness of HER-2/neu and other clinical predictors of survival in patients with primary brain tumors.
authors.affiliation: Department of Internal Medicine, Division of Oncology, University of North Dakota School of Medicine and Health Sciences, Fargo, North Dakota, USA. apotti@medicine.nodak.edu
authors.forename: Anil
authors.initials: A
authors.lastname: Potti
authors.forename: Scott E
authors.initials: SE
authors.lastname: Forseen
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Koka
authors.forename: Hassan
authors.initials: H
authors.lastname: Pervez
authors.forename: Michael
authors.initials: M
authors.lastname: Koch
authors.forename: Genise
authors.initials: G
authors.lastname: Fraiman
authors.forename: Syed A
authors.initials: SA
authors.lastname: Mehdi
authors.forename: Ralph
authors.initials: R
authors.lastname: Levitt
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases