VASCULAR ENDOTHELIAL GROWTH-FACTOR EXPRESSION AND VASCULAR DENSITY ASPROGNOSTIC MARKERS OF SURVIVAL IN PATIENTS WITH LOW-GRADE ASTROCYTOMA

It has long been recognized that some patients with low-gr ade astrocy toma may survive for many years, whereas in others the disease follows a more malignant course resulting in a short survival time, usually d ue to malignant trans formation into higher-grade tumors. Object. The aim of this study was to investigate angiogenesis in the initial biops y specimen of tumor tissue as a biological marker to identify patients with low-grade astrocytoma who are at high risk of malignant tumor tr ansformation or death. Methods. Tumor tissue was studied in 74 consecu tively treated adult patients in whom a diagnosis of diffuse supratent orial hemispheric histologically proven fibrillary low-grade astrocyto ma was made and who underwent surgery between January 1972 and January 1994. Studies were conducted using monoclonal antibodies to the antig ens of the proliferation-associated Ki-67 (MIB-1), factor VIII, vascul ar endothelial growth factor (VEGF), basic fibroblast growth factor (b FGF), and epidermal growth factor (EGF). The overall 5-year survival r ate for the entire patient population was 65%, with a median survival time of 7.5 years. The total mean follow-up period was 6.1 years. All tumors showed a low proliferative potential at the time of the initial operation, as demonstrated by an MIB-1 labeling index of less than 1. 5%. Patients with more than seven microvessels in tumor tissue (29 cas es) had a shorter survival time (mean 3.8 years) than those with seven or fewer microvessels (mean survival 11.2 years). This difference in survival times was significant by univariate (p = 0.001) and stepwise multivariate analyses (p < 0.001). Tumors with a larger number of micr ovessels also had a greater chance of undergoing malignant transformat ion (p = 0.001). Similarly, significant staining for VEGF was correlat ed with shorter survival times when using univariate (p = 0.003) and m ultivariate (p = 0.008) analyses and with a greater chance of malignan t transformation (p = 0.002). Patients with tumors staining positive f or VEGF (39 individuals) had a median survival time of 5.3 years, and those with tumors negative for VEGF (35 patients) had a median surviva l time of 11.2 years. No association was observed between bFGF, EGF, a nd survival or malignant transformation. The stepwise multivariate ana lysis included histological and clinical variables simultaneously. Con clusions. The authors have shown that microvessel density and VEGF lev els are independent prognostic markers of survival in fibrillary low-g rade astrocytoma. This finding leads them to propose that fibrillary d iffuse low-grade astrocytoma is not a single pathological entity but i s composed of a spectrum of tumors with differing propensities to unde rgo malignant transformation that is at least partly based on their in herent angiogenic potential.