Determination of HER-2/neu overexpression and clinical predictors of survival in a cohort of 347 patients with primary malignant brain tumors.

Introduction: 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.

Materials And 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.