Endothelin B receptor expression in human astrocytoma: association with clinicopathological variables and survival...

The endothelin (ET) axis has been implicated in astrocytoma growth and progression. Selective ETB receptor antagonists blocked proliferation and induced apoptosis in astrocytoma cell lines, suggesting that the ETB receptor could be a therapeutic target for astrocytomas. In the present study, we explored the association of the ETB receptor expression with clinicopathological variables and the prognosis of human astrocytomas, by examining the ETB receptor expression and Ki-67 staining in 71 surgically resected astrocytomas with immunohistochemistry. High expression of the ETB receptor was significantly associated with high grade of astrocytomas (p < .0001) and high Ki-67 labeling index (LI; p < .0001). Kaplan-Meier survival analysis showed that the ETB receptor high expression group had significantly shorter disease-free survival (DFS) and overall survival (OS) rates than the low expression group (p < .001). Multivariate analysis with the Cox's proportional hazards model revealed that high expression of the ETB receptor, high WHO grade, and high Ki-67 LI were independent factors for shorter DFS and OS (p < .05 for each comparison). In conclusion, high expression of the ETB receptor is closely associated with high malignancy and poor prognosis of human astrocytomas, which suggests that the ETB receptor could be a promising therapeutic target for astrocytomas, particularly high-grade astrocytomas.