Abstract
CD59 (protectin) and CD46 (membrane cofactor protein, MCP) are membrane-bound complement regulator proteins which inhibit complement-mediated cytolysis of autologous cells. CD59, a phosphatidyl-inositol-anchored glycoprotein, inhibits the formation of the terminal membrane attack complex (MAC) of complement and was found to be a second ligand for CD2 contributing to T-cell activation. In 20 colorectal normal mucosa samples, in ten adenomas, 71 carcinomas and in ten liver metastases derived thereof, CD59 was inconsistently expressed in the epithelial compartment. In carcinomas CD59 expression in the whole neoplastic compartment was more often found in well- and moderately differentiated tumours. By contrast, focal expression or even complete lack of CD59 was more often found in poorly differentiated tumours (P = 0.021). In addition, carcinomas without metastases at the time of operation (Dukes A/B) more often expressed CD59 in the entire neoplastic population compared to those carcinomas which had already metastasised (P = 0.018). There was no correlation between the mode of CD59 expression in colorectal carcinomas and the tumour type or location. CD46 has C3b/C4b binding and factor-I dependent cofactor activity and is broadly expressed in various cells and tissues. In the epithelial compartment of normal colorectal mucosa, of all adenomas, carcinomas and their liver metastases, CD46 was expressed throughout the epithelial compartment. Since CD46 was consistently expressed in colorectal carcinomas the low expression or even lack of CD59 in a subset of tumours might not lead to critical complement-mediated attack of CD59-negative tumour cells. Regarding CD59 as a natural T-cell ligand involved in cognate T-cell-target-cell interaction, however, loss of CD59 might well be a selection advantage, provided that tumour antigen-mediated T-cell toxicity in colorectal carcinoma exists.
Highlights
Tissues and cells Tissue samples from patients who underwent tumour resection of the colon or rectum reached our laboratory within I h after removal. These samples were obtained from cancers, from unaffected mucosa and from adenomas found in the removed specimens
CD59 In normal colorectal mucosa CD59 was inconsistently expressed in the epithelium. 7/20 cases expressed
3/20 mucosae expressed CD59 only in about half of the epithelial compartments; 10 samples entirely lacked CD59 (Table I). Despite this heterogeneous expression of CD59 in the epithelium, CD59 was broadly expressed in the sessile and mobile cells of the gut wall
Summary
Tissues and cells Tissue samples from patients who underwent tumour resection of the colon or rectum reached our laboratory within I h after removal. These samples were obtained from cancers, from unaffected mucosa and from adenomas found in the removed specimens. They were quickfrozen in liquid nitrogen and stored at - 70°C until sectioning. The collection comprised 20 tissue samples of unaffected mucosa, ten adenomas, 71 carcinomas and ten associated liver metastases. Seventeen carcinomas were located at the right side of the colon and 54 at the left side
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