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.

The purpose was to develop a metastatic score specific to the hepatic and peritoneal site in colorectal cancer patients from clinical, pathohistological and molecular markers potentially reflecting oncogenic activation (OA) or epithelial-mesenchymal transition (EMT), where OA may reflect an activation and EMT the functional loss of certain genes. The primary tumour stage (OA, EMT), lymphonodal stage (OA), the presence of a lymphangiosis carcinomatosa (OA), histological grade (OA, EMT), and immunoblot extraction of E-cadherin (OA, EMT) were differentially rated with zero to one or two points due to their potential contribution to each process and the resulting scores were validated in 27 colorectal cancer patients (three patients with pre-malignant adenomas, 16 with primaries and two with local recurrencies, three of which were metastatic to the peritoneum, six metastatic to the liver and two metastatic to both, the liver and the peritoneum, and five with hepatic secondaries, one of which at histology was metastatic to the peritoneum too). As a single parameter only the N-stage significantly contributed to OA (p<0.05). Median OA and EMT scores, however, were 3.5 and 2 in the case of primaries without further spread, 5 and 4 in those nodal positive, 5 and 4 in the case of peritoneal implants, 6 and 2 in the case of liver metastases, and 6.5 and 3 in the case of a simultaneous hepatic and peritoneal spread, respectively. These differences were significant when scores from patients with and without liver metastases (OA, p<0.002) or with peritoneal implants and isolated hepatic spread (EMT, p<0.01) were compared. The results suggest a site-specific contribution of OA and EMT to tumour progression in human colon cancer.

Cancer metastasis results from positive and negative cellular events such as constitutive activation of oncogenes (cOA) or genetic losses (GL) being modulated by downstream signals of epithelial-mesenchymal or mesenchymal-epithelial transition, thus constituting master programs of metastatic phenotype and site specificity. To address the complex nature of these programs, we introduced clinical and phenotypic markers like tumor size, grade, cellular shape, or expression of E-cadherin in 27 colon cancer (CC) patients (cOA and GL), and 41 patients with gastrointestinal stromal tumors (GIST, cOA) to produce scores of cOA and GL. Scores of cOA were highest in case of hepatic and lower in case of an isolated peritoneal spread (GIST), or (CC) of both, cOA and GL, highest in case of a combined hepatic and peritoneal spread and lower in case of an isolated peritoneal spread; but in case of an isolated hepatic spread, scores of cOA were high and low of GL. This indicates a differential contribution of cellular dissociation and recognition in site-specific metastasis, of cOA predominantly in production of hepatic and in the case of GL of serosal spread.

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