Expression of the Endothelin Axis in Bladder Cancer: Relationship to Clinicopathologic Parameters and Long-term Survival

Abstract

Objectives: Endothelin-1 (ET-1) and its receptors ET AR and ET BR, referred to as the Endothelin-axis, play an emerging role in cancer. We examined the ET-axis immunohistochemically in invasive bladder cancer. Methods: Tumor specimens from 157 patients after cystectomy were stained immunohistochemically for ET-1, ET AR and ET BR. After semiquantitative analysis the staining results were correlated with clinicopathological parameters and survival rates. Results: Overexpression of ET-1, ET AR and ET BR was identified in 26.8%, 58.8% and 76.9% of cases, respectively. No association with TNM staging and histologic grading was found. However, patients with ET BR expression tended to have organ-confined tumors ( p = 0.16) and no vascular invasion ( p = 0.09), the latter being statistically significant in the subgroup of G3 tumors ( p = 0.02). ET BR overexpression was associated with favorable disease-free survival ( p = 0.04). Conclusions: The ET-axis is overexpressed in bladder cancer, ET BR predominating in this entity and being associated with a more favorable prognosis. Further studies are warranted to elucidate the role of the ET-axis as a molecular target in bladder cancer.