Increased expression of
sialyl Lewis antigens, sLe(a) and
sLe(x), is frequent during malignant transformation and
tumor progression of
gastrointestinal 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
disease progression of
ductal carcinoma of the pancreas, immunohistochemical expressions of
sLe(x) and sLe(a) in 51
ductal carcinomas of the pancreas were examined. We also examined the expression of
glycosyltransferase genes, which are involved in the synthetic pathways of these
antigens to understand the molecular mechanism involved in the increased expression of these
antigens. 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 significant 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 sLe(a) and
sLe(x)
antigens, patient survival tended to be worse in the
antigens-positive group than in the
antigens-negative group. Increased expression, however, was not dependent on the increased expression of a single
glycosyltransferase gene examined among five such genes, which are postulated to be responsible for the synthesis of the sLe(a) and
sLe(x)
epitopes in the glycosylation pathway. Furthermore, the increased expression of these
antigens was not closely associated with mutations status of the K-ras or p53 genes. These findings suggested that increased expression of
sialyl Lewis antigens are involved in pancreatic
tumorigenesis and that the accumulation of genetic alterations or epigenetic changes is responsible for the molecular mechanisms of increased expression of the sLe(a) and
sLe(x)
antigens in
ductal carcinomas of pancreas.