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

BACKGROUND: The endothelin axis has been shown to have a pivotal role in several human malignancies. The aim of this study was to clarify the clinical importance of endothelin receptor type B (ETBR) in human oesophageal squamous cell carcinoma (OSCC). METHODS: We evaluated ETBR expression in 107 patients with OSCC by immunohistochemistry. Microvessel density (MVD) and lymphatic vessel density were assessed by CD31 and D2-40 immunostaining, respectively. Furthermore, CD4, CD8, and CD45RO+ tumour-infiltrating lymphocytes (TILs) were immunohistochemically analysed. RESULTS: Sixty-one (57%) cases showed high expression of ETBR. Endothelin receptor type B expression was correlated with several clinicopathological factors including tumour differentiation, tumour depth, and lymph node metastasis. The overall and disease-specific survival rates were significantly lower in patients with high ETBR expression than patients with low expression. Furthermore, multivariate analysis revealed that ETBR status was an independent prognostic factor for patient survival. Mechanistic analysis indicated that MVD was significantly higher in tumour tissues with high ETBR expression compared with those with low expression, suggesting that angiogenesis may be a key mechanism in tumour progression and metastasis of OSCC mediated by ETBR expression. By contrast, there were no significant correlations between TILs and ETBR expression. CONCLUSION: Endothelin receptor type B has a pivotal role in oesophageal cancer and may be therapeutic target for this intractable malignancy.