Synthesis and expression of CDw75 antigen in human colorectal cancer

Abstract

BackgroundIncreased ST6Gal I activity has been associated with the α(2,6)sialylation enhancement of membrane glycoconjugates observed in metastatic colorectal carcinomas (CRC). Siaα(2,6)Galβ(1,4)GlcNAc sequence, known as CDw75, is a sialylated carbohydrate determinant generated by the ST6Gal I. This epitope has been reported to be associated with the progression of gastric and colorectal tumours, hence there are only a few conclusive studies to date.MethodsBy radioisotopic techniques we evaluated the ST6Gal I activity in healthy, transitional and tumour tissues from 43 patients with CRC. By immunohistochemistry we assessed the CDw75 expression in 25 colorectal adenomas, 43 tumours, 13 transitional and 28 healthy tissues of CRC patients.ResultsST6Gal I activity was likewise found to be statistically higher in tumour tissue respect to healthy tissue from CRC patients. CDw75 expression was positive in 20% of colorectal adenomas. Furthermore, 70% of tumour specimens and 8.3% of transitional specimens were positive for CDw75 expression, whereas none of the healthy ones showed the presence of the epitope.ConclusionThe major contribution of this study is the inclusion of data from transitional tissue and the analysis of CDw75 antigen expression in CRC and in colorectal adenomas, little known so far. ST6Gal I activity and CDw75 antigen expression were increased in CRC. Although their comparison did not reach the statistical significance, a great extent of patients showed both, an enhanced tumour ST6Gal I activity and an increased CDw75 expression in the tumour tissue. So, these two variables may play a role in malignant transformation. The expression of CDw75 in colorectal adenomas suggests that this antigen may be a tumour marker in CRC.

Disease-Free Survival of Colorectal Cancer Patients in Relation to CDw75 Antigen Expression

“…The expression detected in this tissue could be related to the tumour process since we have not observed expression of CDw75 in colorectal mucosa from disease-free patients. Concerning the colorectal adenomas, we detected expression of CDw75 antigen in 26% of the specimens, similar to our previous observations [22] in a study in which a smaller number of adenomas were analyzed. The majority of the adenomas showed weak CDw75 expression and the correlation analysis between the expression and the clinicopathological features did not reveal any association.…”

“…In a previous study, we reported enhanced CDw75 expression in CRC specimens compared with healthy colorectal specimens [22] . The main objective of this work was to study the influence of CDw75 expression in tumour recurrences in patients with CRC.…”

“…In a recent study, our group reported an increase in both CDw75 expression and ST6Gal I activity in CRC, as well as a possible implication of CDw75 in CRC development [22] . In the present study, we examined whether the expression of CDw75 antigen in CRC is associated with tumour recurrence.…”

Identification of proteins with the CDw75 epitope in human colorectal cancer

“…The CDw75 antigen is a ligand for the leukocyte adhesion receptor cluster of differentiation (CD) 22, whose activation leads to the inhibition of intracellular signaling pathways (5). CD22 is located on the B cell membrane and specifically recognizes α(2,6)-linked sialic acid (6,7).…”

“…Furthermore, in CRC patients, ST6Gal I activity is greater in tumor than in healthy tissue (18,19), particularly in metastatic tumors (20). The CDw75 antigen is expressed in the majority of colorectal tumors, where its expression is augmented with regard to the healthy mucosa (21,22). Additionally, CDw75 expression is particularly high in non-polypoid tumors and advanced or metastatic stages of the disease, although results from clinicopathological studies suggest it could represent a good prognosis marker for 3-year overall survival (23).…”