Elevated serum levels of Dupan-2 in pancreatic cancer patients negative for Lewis blood group phenotype

Abstract

Summary CA19-9, a serum marker for pancreatic cancer, gives false-negative results in patients who are negative for the Lewis blood group phenotype. To determine whether other markers may compensate for this drawback, serum levels of CA50, Span-l, sialyl SSEA-1 and Dupan-2 were assayed and compared with those of CA19-9 in 207 normal subjects and in 200 patients with pancreatic carcinoma whose Lewis blood group phenotypes were confirmed. In normal subjects with the Lewis negative phenotype, the serum levels of CA50 and Span-i, as well as CA19-9, were significantly low, whereas those of sialyl SSEA-1 were independent of the Lewis blood group phenotype. Serum levels of Dupan-2 were significantly higher in normal subjects with the Le (a -b -) phenotype as compared with those with Le(a -b +). The sensitivity for pancreatic carcinoma was 81% for CA19-9, 84% for CA50, 82% for Span-i, 51% for sialyl SSEA-1 and 63% for Dupan-2. Among the 39 CA19-9 negative patients, 13 were determined as being Lewis negative by the serum dot-ELISA technique. Although the positive rates were essentially comparable when each marker was combined with CAl9-9, a highly elevated serum level of Dupan-2, which strongly suggested the presence of malignancy, was most frequently encountered in 39 patients who were not diagnosed by CA19-9 assay, especially those with Lewis negative blood groups. With regard to the three other markers, we found few patients with a highly elevated serum level in either the Lewis-negative or -positive groups. We conclude that Dupan-2 tended to be elevated in patients with pancreatic cancer who were negative for the Lewis blood group phenotype.

The Prevalence and Nature of Glycan Alterations on Specific Proteins in Pancreatic Cancer Patients Revealed Using Antibody-Lectin Sandwich Arrays

“…The individuals in this study that were negative for CA 19-9 elevations may represent those genotypes. Other glycans potentially could be used to complement CA 19-9, a strategy previously attempted using various related monoclonal antibodies (47). However, only limited detection of CA 19-9-negative patients was achieved.…”

Glycan Motif Profiling Reveals Plasma Sialyl-Lewis X Elevations in Pancreatic Cancers That Are Negative for Sialyl-Lewis A *

“…Perhaps the most promising antibody for this purpose was DUPAN2. Separate studies demonstrated that some of the CA19 -9-low patients show elevations in DUPAN-2 (20,36), but a biomarker panel based on these assays never became established. Miyamoto and coworkers found increased levels of a novel glycan, 6-sialylated, type-1 H antigen, in three out of six pancreatic tumors that were negative for CA19 -9 (37), but the researchers did not demonstrate this structure as a blood biomarker.…”

Clinicopathological Analysis of DU-PAN-2 as a Tumor Marker for Endometrial Adenocarcinoma in Comparison with CA19-9.

“…DU-PAN-2 and CA19-9 expressions are also involved in ABH (O) antigens synthesis [15]. Since 5~10% of the Japanese population are considered to lack the Le enzyme, CA19-9 is less useful to them as a tumor marker due to its negative expression [6,7,11]. Generally, therefore, individuals negative for Le a and Le b due to a lack of the Le enzyme are anticipated to show an increase of serum DU-PAN-2 in those carcinomas [6,21].…”

“…Since 5~10% of the Japanese population are considered to lack the Le enzyme, CA19-9 is less useful to them as a tumor marker due to its negative expression [6,7,11]. Generally, therefore, individuals negative for Le a and Le b due to a lack of the Le enzyme are anticipated to show an increase of serum DU-PAN-2 in those carcinomas [6,21]. Carbohydrate antigen expressions have been proven to undergo qualitative and quantitative alterations during the normal menstrual cycle and a malignant transformation of the endometrium [1-3, Correspondence to: Masanori Yasuda, MD, Department of Pathology, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan.…”

“…The carbohydrate antigens, recognized by the DU-PAN-2 and CA19-9 antibodies, are defined as sialyl Lewis c (Le c ) and sialyl Lewis a (Le a ), respectively [6,7] (Fig. 1).…”