Background: Microvessel density in tumors, a measure of angiogenesis, has been shown to be a prognostic indicator that correlates with an increased risk of metastasis in various epithelial cancers and with overall and relapse free survival in patients with breast cancer. Astrocytic brain tumors, particularly malignant astrocytomas, are recognized to be highly vascular tumors with potent angiogenic activity. However, the prognostic significance of microvessel density in these tumors is not known.
Methods: Sections from formalin fixed paraffin embedded tumor tissue from 93 unselected adult patients with supratentorial astrocytic brain tumors were immunostained for factor VIII-related antigen in order to highlight microvessel endothelial cells. Microvessels were counted at 200x and 400x magnification. Microvessel density was graded as 1+ to 4+ on 1 low power field, without knowledge of clinical outcome. Microvessel count and microvessel grade were correlated with postoperative survival using the Cox proportional hazards regression model. The prognostic significance of microvessel count and grade were also compared with established prognostic indicators, including patient age, Karnofsky performance status, and tumor histology using multivariate analyses.
Results: Both microvessel grade and microvessel count correlated significantly with postoperative survival by univariate analysis in both previously untreated and treated patients. Patients with tumors containing a microvessel Grade of 3+ or 4+ had significantly shorter survival time than patients with a microvessel Grade of 1+ or 2+ (P = 0.0022). Likewise, patients with microvessel counts of 70 or greater had significantly shorter survival than those with microvessel counts of fewer than 70 (P = 0.041). Patient age, Karnofsky performance status, tumor histology, and extent of resection were also correlated with survival by univariate analysis. Microvessel count was further shown to be an independent prognostic indicator by multivariate analyses. There were correlations between microvessel density and patient age and between microvessel density and astrocytic tumor grade.
Conclusions: These findings support the importance of microvessel density as a prognostic indicator of postoperative survival of patients with astroglial brain tumors. Regional tumor heterogeneity may limit the use of these techniques for routine pathologic examination.