Expression of the endothelin axis in bladder cancer: relationship to clinicopathologic parameters and long-term survival

Eur Urol. 2005 May;47(5):593-600. doi: 10.1016/j.eururo.2004.12.019. Epub 2005 Jan 26.

Abstract

Objectives: Endothelin-1 (ET-1) and its receptors ET(A)R and ET(B)R, 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(A)R and ET(B)R. After semiquantitative analysis the staining results were correlated with clinicopathological parameters and survival rates.

Results: Overexpression of ET-1, ET(A)R and ET(B)R 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(B)R 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(B)R overexpression was associated with favorable disease-free survival (p=0.04).

Conclusions: The ET-axis is overexpressed in bladder cancer, ET(B)R 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Cystectomy
  • Disease-Free Survival
  • Endothelin-1 / biosynthesis*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Receptor, Endothelin A / biosynthesis*
  • Receptor, Endothelin B / biosynthesis*
  • Survival Rate / trends
  • Time Factors
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery

Substances

  • Biomarkers, Tumor
  • Endothelin-1
  • Receptor, Endothelin A
  • Receptor, Endothelin B