Endothelin B Receptor Expression in Human Astrocytoma: Association With Clinicopathological Variables and Survival Outcomes

Abstract

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.

Endothelin B receptor expression correlates with tumour angiogenesis and prognosis in oesophageal squamous cell carcinoma

“…To our knowledge, this is the first report to demonstrate that ETBR is an independent prognostic marker for human oesophageal cancer. Previous studies have also demonstrated that tumour ETBR expression was a negative prognostic marker in other cancers (Shen et al , 2011). On the other hand, ETBR gene expression was reported as a positive prognostic marker in renal cell carcinoma (Wuttig et al , 2012).…”

Overexpression of endothelin B receptor in glioblastoma: a prognostic marker and therapeutic target?

“…The sections were then counterstained with hematoxylin, dried, and mounted with xylene-based mounting medium. Positive staining was graded as low or high as described [ 12 ].…”

“…Overexpression of ETBR in GBM was associated with a poor prognosis in a Chinese population [ 12 ]. Since ethnicity may play a major role in the pathogenesis of gliomas [ 13 , 14 ], we investigated whether ETBR overexpression could be detected in patients with GBM and in other cancers outside of China, whether ETBR expression correlates with patient survival (and thus its potential use as a prognostic marker and/or therapeutic target), and whether clinically available endothelin receptor blockers/antagonists have toxic effects on cancer cells in vitro.…”

Ki-67 is a Valuable Prognostic Factor in Gliomas: Evidence from a Systematic Review and Meta-analysis

“…Of the candidate studies, 13 articles failed to completely describe the available survival data. Finally, 51 published studies in total were included in the analysis after eliminating articles unsatisfying the selection criteria and duplicates (Jaros et al, 1992;Torp et al, 1992;Montine et al, 1994;Ellison et al, 1995;Heegaard et al, 1995;Kros et al, 1996;Coons et al, 1997;Pollack et al, 1997;Dehghani et al, 1998;McKeever et al, 1998;Ritter et al, 1998;Figarella-Branger et al, 2000;Rodriguez-Pereira et al, 2000;Ho et al, 2001;ReaveyCantwell et al, 2001;Zhong et al, 2001;Bredel et al, 2002;Pollack et al, 2002;Bowers, 2003;Chiang et al, 2003;Neder et al, 2003;Wessels et al, 2003;Zamecnik et al, 2003;Preusser et al, 2005;Uematsu et al, 2005;Kleinschmidt-DeMasters et al, 2006;Donato et al, 2007;Kanamori et al, 2008;Kuo et al, 2009;Laks et al, 2009;Li et al, 2009;Armstrong et al, 2010;Nabika et al, 2010;Watanabe et al, 2010;Yoshida et al, 2010;Habberstad et al, 2011;Margraf et al, 2011;Qiang et al, 2011;Shen et al, 2011;Zawrocki et al, 2011;…”