Expression and prognostic relevance of endothelin-B receptor in vulvar cancer

Oncol Rep. 2007 Aug;18(2):305-11.


Overexpression of endothelin (ET)-1 and its receptors, ETAR and ETBR, commonly referred to as the 'ET-axis', has been demonstrated to play a role in cancer progression for various human tumours. Based on these results we propose a similar role of the expression of the ET-axis in vulvar cancer. Expression of the ET-axis was investigated immunohistochemically using tissue microarrays with tumour samples of 68 vulvar cancer patients. Samples were obtained from patients undergoing local excision or radical vulvectomy. ET-1 expression of tumour cells correlated highly significantly with early stages of vulvar cancer (p=0.004), whereas neither ETAR nor ETBR expression showed any association with TNM stages. High staining levels of ETBR in the tumour tissue were significantly related to tumour progression (p=0.01) and early metastases (p=0.09); low ETBR staining intensity correlated with longer relapse-free survival (p=0.019). In patients with ETBR overexpressing low-stage tumours (pT1-2) we observed a significantly reduced overall survival and disease-free survival (p=0.036 and 0.021, respectively). ETAR expression and ETBR expression were significantly correlative (p=0.018). Accordingly, co-expression of both receptors was related to tumour progression (p=0.022) and an increased risk for local recurrence (p=0.005). These results suggest that, in addition to established histological and clinical prognostic factors, analysis of ET-receptor and, in particular, of ETBR expression by means of simple immunohistochemical analysis might improve prediction of the prognosis for patients with vulvar squamous cell carcinoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Disease Progression
  • Endothelin-1 / analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Receptor, Endothelin A / analysis
  • Receptor, Endothelin B / biosynthesis*
  • Survival Analysis
  • Vulvar Neoplasms / metabolism
  • Vulvar Neoplasms / pathology*


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