Soluble serum E-cadherin as a marker of tumour progression in colorectal cancer patients

Abstract

A pilot study was conducted to determine the concentrations of soluble serum E-cadherin in 36 patients with colorectal cancer or a high-grade dysplasia by the use of an ELISA technique. The results were compared with staging characteristics and concentrations of routine serum carcinoembryonic antigen (CEA). Sixteen patients with benign diseases and nine healthy volunteers served as internal or negative controls. Tumour specimens from seven patients were analysed by immunohistochemistry to compare concentrations of soluble serum E-cadherin with patterns of cell-bound E-cadherin or beta-catenin. Serum E-cadherin concentrations were increased in colorectal cancer patients (P = 0.009), but also in benign disease controls (P = 0.005), correlating with the T- (P < 0.05), but not N- or M-stage, and with serum CEA (P = 0.002) in case of existing liver metastases. Compared with other staining patterns, concentrations of soluble serum E-cadherin were higher in case of an exclusive membrane-bound localization of cellular beta-catenin (P = 0.071). The results suggest marker characteristics of soluble serum E-cadherin in colorectal cancer patients, but lacking specificity argues against a routine clinical use.

Soluble E-cadherin: more than a symptom of disease

“…Later, Willmanns et al found that sE-cad levels were statistically different between healthy controls versus benign disease ( P = 0.005) versus cancer ( P = 0.009) (3,476 ng/ml; 5,248 ng/ml; 5,495 ng/ml) and that the highest levels were found in metastatic patients (79). They also observed that in this cancer cohort, patients with renal or hepatic failure had high levels of sE-cad and that patients who had been treated with chemotherapy had lower sE-cad levels compared to untreated patients (79). From these data, it is apparent that while sE-cad serum levels may be useful in determining cancer spread in untreated patients, it would be important to rule out organ failure or dysfunction.…”

Clinical Significance of Serum Soluble E-cadherin in Colorectal Carcinoma

“…Soluble E-cadherin (sE-cadherin) is a degradation product of E-cadherin produced by ectodomain shedding that was first detected in the serum and urine of healthy individuals, and increased levels have been attributed to a variety of diseases, in particular to neoplasms of epithelial origin [14][15][16][17][18][19][20][21][22][23]. Wilmanns et al demonstrated that increased serum sE-cadherin concentrations in CRC patients were correlated with T classification and reflected further disease extension in some patients with lymph node and distant metastasis [18].…”

“…Wilmanns et al demonstrated that increased serum sE-cadherin concentrations in CRC patients were correlated with T classification and reflected further disease extension in some patients with lymph node and distant metastasis [18]. Recently, Weiss et al reported that serum sE-cadherin was significantly increased in patients with stages III and IV carcinomas, and suggested a potential application of sE-cadherin as an alternative diagnostic biomarker for monitoring disease progression [24].…”

The Ectodomain Shedding of E-cadherin by ADAM15 Supports ErbB Receptor Activation

“…E-cadherin disruption has been observed in multiple pathophysiological conditions, including inflammation and cancer (5). In fact, E-cadherin is considered to function as a metastasis suppressor due to its inhibition of cancer cell migration and invasion (6). Several proteases have been implicated in the extracellular cleavage of E-cadherin, including MMP3, MMP7, MT1-MMP, plasmin, kallikrein 7, and ADAM10.…”