Raised levels of plasma big endothelin 1 in patients with colorectal cancer

Abstract
Background: The aim was to assess the role of plasma Big Endothelin (ET) 1 levels as a marker of disease presence and stage in colorectal adenocarcinoma. Methods: Big ET-1 was measured in the plasma of 37 patients with colorectal cancer. Preoperative systemic plasma levels of Big ET-1 in patients with cancer were compared with levels in 20 age- and sex-matched controls. Portal plasma samples were collected at operation in addition to peripheral venous samples. Immunohistochemical staining for Big ET-1 was performed on a selection of primary tumour specimens and liver metastases. Results: Median (range) preoperative systemic plasma levels of Big ET-1 were significantly higher in patients with cancer than in controls (1·0 (0·3–9·7) versus 0·2 (0·0–6·0) fmol/ml; P = 0·0001). Intraoperative portal plasma levels of Big ET-1 were significantly higher in patients with Dukes' ‘D’ disease than in patients with Dukes' A, B and C disease (2·1 (1·4–10·0) versus 1·2 (0·3–6·6) fmol/ml; P = 0·01). Similarly, systemic plasma levels were significantly higher in patients with Dukes' ‘D’ disease than in those with localized disease (1·9 (1·2–9·7) versus 1·2 (0·2–8·3) fmol/ml; P = 0·01). The presence of microvascular invasion in the tumour specimens was associated with a significantly raised portal plasma level of Big ET-1 (1·6 (1·5–2·1) versus 1·1 (0·8–1·3) fmol/ml; P = 0·04). Immunohistochemistry localized Big ET-1 to the cancer epithelial cells. Conclusion: The plasma level of Big ET-1 is significantly raised in patients with colorectal cancer. Patients with liver metastases have significantly higher levels than those with localized disease.