Overexpression of Sialyl Lewis x Antigen Is Associated with Formation of Extratumoral Venous Invasion and Predicts Postoperative Development of Massive Hepatic Metastasis in Cases with Pancreatic Ductal Adenocarcinoma

Abstract

The clinicopathological factors and expression of sialyl Lewis antigens which are the cell adhesion molecules to endothelial cells were compared in relation to the extent of the postoperative hepatic metastasis in 23 consecutive patients with pancreatic ductal adenocarcinoma whose clinical courses were carefully monitored and documented. The overall survival of cases with massive hepatic metastasis (MHM) was significantly poorer than that of those with local or no hepatic metastasis (p = 0.0453). Postoperative MHM was significantly correlated with the presence of duodenal invasion (p = 0.0418), the presence of portal vein invasion (p = 0.0435), the presence of extratumoral venous invasion (p = 0.0052) and high expression of sialyl Lewis x antigen (p = 0.0022). Multivariate analysis confined significant correlation between the high expression of sialyl Lewis x antigen and the development of MHM (p = 0.0402). Kaplan-Meier analysis revealed that the overall survival of patients with a high expression of sialyl Lewis x antigen was significantly poorer than that of patients with a low expression of the antigen (p = 0.0216). These results indicate that the overexpression of sialyl Lewis x antigen plays an important role in the development of MHM, and also predicts a poorer overall survival of these patients. Further studies with more cases are warranted to confirm these results.

Sialofucosylated podocalyxin is a functional E- and L-selectin ligand expressed by metastatic pancreatic cancer cells

“…It is believed that a variety of tumor cells, including those from pancreatic cancers, express sialofucosylated molecules that can bind to selectins under shear flow (26,33,42,46). While sLe x is absent from normal pancreatic tissue (35, 37), its expression progressively increases with higher-grade pancreatic intraepithelial neoplasia and pancreatic adenocarcinoma and correlates with massive metastasis and poor prognosis in humans (1,2,36,43).Podocalyxin (PODXL) is a transmembrane protein that is expressed by a number of human cell types such as hematopoietic progenitors, platelets, and vascular endothelial cells (11,15,30,32). PODXL was first identified in the kidney, where it helps form a highly negatively charged cell surface coat that maintains the filtration slit in the glomerulus (21).…”

Prognostic Value of Multimarker Analysis in Stage III Colorectal Cancer: One Step Forward Towards an Individualized Therapy Decision

“…chromogranin A) as well as markers of the small synaptic vesicles (for example synaptophysin) has been proven valuable and sufficient to identify neuroendocrine dif- ferentiation of CRC in different groups of patients [30,31]. Sialyl-Le x is associated with extra-tumoral venous invasion [14] and represents an interesting target for tumor identification. The peripheral benzodiazepine receptor (PBR) is another important prognostic marker and is associated with a more aggressive tumor type [11,17].…”

“…Sialyl-Le x antigen is a modified blood group antigen which was found to be overexpressed in different malignant tissues [13]. Its presence was associated with formation of extratumoral venous invasion [14], tumor progression and a metastatic phenotype [15]. The tumor suppressor gene p53 and its transitional target gene BAX [16], a proapoptotic member of the Bcl-2 family, are known regulators of apoptosis induced by cytostatic drugs.…”

The role of adhesion molecules in acute myeloid leukemia and (hemato)oncology: A systematic review

“…New insights on adhesive interactions and the prognostic relevance of tumor CD24 expression have been recently documented for various nonhematological malignancies [37][38][39][40][41][42][43] . Knowledge of sLe X mediated adhesive interactions with endothelial cells and platelets is important for understanding the pathophysiology of tumor metastasis [44][45][46][47][48] . Both CD24 and CD44 molecules that serve as selectin ligands are strongly expressed in solid tumors.…”

“…Both CD24 and CD44 molecules that serve as selectin ligands are strongly expressed in solid tumors. In postresection patients, an inverse correlation between survival and sLe X expression in tumor cells was found [48][49][50][51] . P-selectin deficient mice showed slower growth of subcutaneously implanted human colon carcinoma cells and generated fewer lung metastases after intravenous administration.…”