Apoptosis and survival in high-grade astrocytomas as related to tumor Fas (APO-1/CD95) expression.

Abstract

Although a majority of high-grade gliomas express the apoptosis-inducing receptor Fas, little is known about the extent of apoptosis or prognostic significance of Fas expression in these tumors. In situ labeling of apoptotic cells and Ki-67 immunohistochemistry were performed on 51 high-grade human astrocytomas previously characterized for Fas expression. Survival data was compiled from patient records and correlated with tumor grade, apoptotic index (AI) and Fas expression. A significant correlation was found between tumor grade and the AI and Ki-67 labeling index (LI); however, only the AI increased significantly with Fas expression. The AI increased from 0.39 +/- 0.12% to 0.82 +/- 0.10% in grade III vs. IV astrocytomas (P = 0.003). The Ki-67-LI increased from 3.64 +/- 1.5% to 11.35 +/- 2.1% in grade III vs. IV astrocytomas (P = 0.004). Additionally, tumors expressing higher Fas levels had a greater AI than those expressing lower levels (0.81 +/- 0.11% vs. 0.43 +/- 0.11%) (P = 0.017). Despite longer median survivals for patients with tumors exhibiting high Fas expression, statistical significance was not achieved. Patients with grade III astrocytomas demonstrated a median survival of 20 vs. 18 months for tumors with high vs. low Fas expression (P = 0.51). Patients with grade IV astrocytomas demonstrated a median survival of 9 vs. 7.4 months for tumors with high vs. low Fas expression, respectively (P = 0.77). Although the degree of Fas expression in high-grade astrocytomas appears to correlate with the apoptotic rate, no overall differences in survival could be demonstrated between tumors expressing high vs. low Fas levels.