Molecular mechanism involved 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 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.
Nakamori
S
S
Dept. of Surgery II, Osaka University Medical School, Suita, Japan. nakamori@surg2.med.osaka-u.ac.jp
Nishihara
S
S
Ikehara
Y
Y
Nagano
H
H
Dono
K
K
Sakon
M
M
Narimatsu
H
H
Monden
M
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D018395:CA-19-9 Antigen; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005732:Gangliosides / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D011905:Genes, ras; D006031:Glycosylation; D016695:Glycosyltransferases / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D000080506:Sialyl Lewis X Antigen; D016019:Survival Analysis
D000951:Antigens, Neoplasm; D018395:CA-19-9 Antigen; D005732:Gangliosides; D009363:Neoplasm Proteins; D000080506:Sialyl Lewis X Antigen; C094688:sialyl Lewis(x) ganglioside; C064564:sialyl Le(a) ganglioside; D016695:Glycosyltransferases