Molecular mechanism involoved in increased expression of sialyl Lewis antigens in ductal carcinoma of the pancreas

Increased expression of sialyl Lewis antigens, sLe(a) and sLe(x), is freque nt during malignant transformation and tumor progression of gastrointestina l cancers and it is assumed to be correlated with the increased metastatic potential of tumor cells and, consequently, with poor patient survival. To determine the influence of the increased expression of these antigens in di sease progression of ductal carcinoma of the pancreas, immunohistochemical expressions of sLe(x) and sLe(a) in 51 ductal carcinomas of the pancreas we re examined. We also examined the expression of glycosyltransferase genes, which are involved in the synthetic pathways of these antigens to understan d the molecular mechanism involved in the increased expression of these ant igens. Of the 51 primary ductal carcinomas of the pancreas, 40 (78.4%) were sLe(a)-positive and 11 (21.6%) were sLe(a)-negative; 16 (31.4%) were sLe(x )-positive and 35 (68.6%) were sLe(x)-negative, Although there were no sign ificant differences in any examined clinicopathological factors such as age , sex, histological type, tumor size, presence of lymph node metastasis, or presence of vessel invasion between the positive and negative groups with both the sLea and sLex antigens, patient survival tended to be worse in the antigens-positive group than in the antigens-negative group. Increased exp ression, however, was not dependent on the increased expression of a single glycosyltransferase gene examined among five such genes, which are postula ted to be responsible for the synthesis of the sLe(a) and sLe(x) epitopes i n the glyosylation pathway. Furthermore, the increased expression of these antigens was not closely associated with mutations status of the K-ras or p 53 genes. These findings suggested that increased expression of sialyl Lewi s antigens are involved in pancreatic tumorigenesis and that the accumulati on of genetic alterations or epigenetic changes is responsible for the mole cular mechanisms of increased expression of the sLe(a) and sLe(x) antigens in ductal carcinomas of pancreas.