lewis-x-antigen and Pancreatic-Neoplasms

This review is concerned with the usefulness and the problem of biomarkers for cancer of digestive organs. Carcinoembryonic antigen (CEA) is a most popular and useful tumor marker for cancer of digestive organs. Squamous cell carcinoma (SCC) antigen and CYFRA have been reported as a useful tumor marker for esophageal cancer. CEA and CA 19-9 are a good prognostic factor in gastric cancer patients. The post-operative increase of serum CEA can be a predictive marker for the patients of colorectal cancer. Development of a radioimmunoassay for highly sensitive detection of tumor markers, they are considered to be useful for monitoring after treatment. But are not useful for the early diagnosis. The diagnosis of hepatocellular carcinoma (HCC) is based mainly on serological markers, such as alpha-fetoprotein and PIVKA-II. The two are useful complementary markers of HCC because they do not correlate with each other. But the problem of the false-positive rate for the patients with chronic hepatitis or liver cirrhosis is still remained. A typical marker of pancreatic and bile duct cancer is carbohydrate antigen, but the sensitivity of these markers is only 50%. Recent molecular biological analysis may be used as effective biomarkers in the diagnosis, prognosis, therapy, and risk assessment of digestive cancer.

Topics: alpha-Fetoproteins; Antigens, CD19; Antigens, Neoplasm; Biomarkers; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Colorectal Neoplasms; Digestive System Neoplasms; Esophageal Neoplasms; Female; Humans; Keratin-19; Keratins; Lewis X Antigen; Liver Neoplasms; Pancreatic Neoplasms; Prognosis; Protein Precursors; Prothrombin; Stomach Neoplasms

Topics: Biomarkers, Tumor; Female; Humans; Lewis X Antigen; Lung Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms

Most of the recently developed tumor antigens detected by monoclonal antibodies are sugar chains and frequently associated with blood group substance. By immunohistochemical studies, we evaluated mainly the clinical usefulness and significance of the serum assay of CA-50 classified as a type 1 sugar chain, sialyl SSEA-1 as a type 2 sugar chain, and ST-439 with an undetermined structure, as well as their clinicopathological significance. In addition, the value of measurement of CA19-9, ST-439, and SLX in pure pancreatic juice (PPJ) was investigated. Furthermore, the clinical usefulness of K-ras mutation at codon 12 (KRM) in PPJ was studied. The incidence of serum CA19-9 among tumor markers was highest in pancreatic cancer (81%), but relatively high in benign diseases. On the other hand, both serological and immunohistological studies showed that sialyl SSEA-1 and ST-439 were highly specific for the tumor, whereas they appeared in serum or tumor less frequently than CA19-9 or CA-50 carrying the type 1 sugar chain. The accuracy of the tumor markers (CA19-9, sialyl SSEA-1, and ST-439) for pancreatic cancer, was almost equal (77% to 80%) and higher than that of CEA (69%). However, a highly positive correlation between sialyl SSEA-1 and ST-439 was revealed as well as among type 1 sugar chains in malignant diseases. Therefore, we conclude that the combination assay with CA19-9 or a similar tumor marker, sialyl SSEA-1 or ST-439, and CEA would be appropriate for the screening of pancreatic cancer. When the cut off value was set as the M + 2SD of the controls, significantly elevated concentrations of CA19-9 in PPJ were found in the secretory phase in 90% of the patients with pancreatic cancer (PC) and 66% of the patients with chronic pancreatitis (CP). Although increased concentrations of CA19-9 in PPJ have no cancer specificity, measurement of CA19-9 in PPJ can be used as a sensitive marker for some pancreatic disorders. On the other hand, concentrations of ST-439 and SLX in PPJ were significantly increased only in PC, and their incidences were 50% and 40%, respectively. They have a high tumor-specificity, but their incidences were not as high as initially expected.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Codon; Female; Genes, ras; Humans; Lewis X Antigen; Male; Mutation; Pancreatic Neoplasms; Polymerase Chain Reaction

A radioimmunological analysis of the changes in concentration of tumour markers CA 19-9, REA, beta 2-microglobulin, trypsin and C-peptide was carried out in 53 patients with pancreatic cancer and in 14 patients with cancer of the major duodenal papilla before and 7-10 days after the treatment. A control group was comprised of 116 volunteers. The levels of the tumour markers decreased after the combined use of remote radiotherapy and pancreaticoduodenal resection (PDR). After creation of cholecysto-enteroanastomosis and performance of radiotherapy they remained without changes. Exocrine pancreatic function after remote radiotherapy, especially in combination with PDR, was sharply suppressed.

Topics: Ampulla of Vater; beta 2-Microglobulin; Biomarkers, Tumor; C-Peptide; CA-19-9 Antigen; Combined Modality Therapy; Common Bile Duct Neoplasms; Humans; Lewis X Antigen; Pancreatic Neoplasms; Prohibitins; Radioimmunoassay; Surgical Procedures, Operative; Time Factors; Treatment Outcome; Trypsin

The study was performed to identify unique subtype from the long-term survival (>24 months) patients with advanced pancreatic cancer (1039 cases). Long-term survival patients had higher proportion of low secretion of carbohydrate antigen 19-9 (CA19-9) than that of patients with non long-term survival (P < 0.001). Considering the impact of Lewis status on CA19-9 secretion, Lewis genotypes were further determined by Sanger sequencing. The prognosis of CA19-9-Low&Lewis (-) patients was worse than that of CA19-9-Low&Lewis (+) (hazard ratio (HR) = 0.37, P < 0.001). The proportion of epidermal growth factor receptor (EGFR) (-) cases was lower in the CA19-9-Low&Lewis (+) subgroup than that in other patients (P = 0.047). For the CA19-9-Low&Lewis (+) subgroup, chemotherapy plus radiotherapy but not chemotherapy was found to be an independent prognostic factor (versus best supportive care, chemotherapy, HR = 0.71, P = 0.267; chemotherapy plus radiotherapy, HR = 0.33, P = 0.022). We conclude that CA19-9-Low&Lewis (+) pancreatic cancer is a unique subtype with special biological properties.

Topics: Adenocarcinoma; Antineoplastic Agents; CA-19-9 Antigen; Chemoradiotherapy; Chi-Square Distribution; Databases, Factual; Female; Fucosyltransferases; Genetic Predisposition to Disease; Humans; Kaplan-Meier Estimate; Lewis X Antigen; Male; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Phenotype; Proportional Hazards Models; Risk Factors; Survivors; Time Factors; Treatment Outcome

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant stroma containing several pro-inflammatory cytokines, which are described to modulate the expression of important genes related to tumor promotion and progression. In the present work we have investigated the potential role of these cytokines in the biosynthesis of tumor-associated carbohydrate antigens such as sialyl-Lewis(x) (SLe(x)) through the regulation of specific glycosyltransferase genes.. Two human PDAC cell lines MDAPanc-3 and MDAPanc-28 were treated with pro-inflammatory cytokines IL-1β, TNFα, IL-6 or IL-8, and the content of tumor-associated carbohydrate antigens at the cell membrane was analyzed by flow cytometry. In addition, variation in the mRNA expression of sialyltransferase (ST) and fucosyltransferase (FUT) genes, which codify for the ST and FucT enzymes involved in the carbohydrate antigens' biosynthesis, was determined. The inflammatory microenvironment of PDAC tissues and the expression of Lewis-type antigens were analyzed by immunohistochemistry to find a possible correlation between inflammation status and the presence of tumor-associated carbohydrate antigens.. IL-1β stimuli increased SLe(x) and α2,6-sialic acid levels in MDAPanc-28 cells and enhanced the mRNA levels of ST3GAL3-4 and FUT5-7, which codify for ST and FucT enzymes related to SLe(x) biosynthesis, and of ST6GAL1. IL-6 and TNFα treatments increased the levels of SLe(x) and Le(y) antigens in MDPanc-3 cells and, similarly, the mRNA expression of ST3GAL3-4, FUT1-2 and FUT6, related to these Lewis-type antigens' biosynthesis, were increased. Most PDAC tissues stained for SLe(x) and SLe(a) and tended to be expressed in the tumor samples with a higher presence of inflammatory immune cells.. The inflammatory microenvironment can modulate the glycosylation pattern of PDAC cells, increasing the expression of tumor-associated sialylated antigens such as SLe(x), which contributes to pancreatic tumor malignancy.

Topics: Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Cytokines; Disease Progression; Epitopes; Flow Cytometry; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glycosyltransferases; Humans; Immunohistochemistry; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Lewis X Antigen; Oligosaccharides; Pancreatic Neoplasms; Polysaccharides; Sialic Acids; Sialyl Lewis X Antigen; Tumor Necrosis Factor-alpha

Topics: Biomarkers, Tumor; Female; Humans; Lewis X Antigen; Lung Neoplasms; Male; Ovarian Neoplasms; Pancreatic Neoplasms; Sialyl Lewis X Antigen

Peritoneal dissemination and hepatic metastasis commonly occur after patients with pancreatic cancer have undergone surgery. It is thought that specific adhesion molecules play corresponding roles in cancer metastasis.. We conducted in vitro and in vivo studies to assess the role of adhesion molecules in these processes, using SW1990 cells derived from human pancreatic cancer.. SW1990 cells pronouncedly expressed sialyl Lewis(a) (s-Le[a]) and sialyl Lewis(x) antigens (s-Le[x]), CD44H, and beta1 integrin. Also, SW1990 cells showed a strong binding activity to IL-1beta activated human umbilical vein endothelial cells, cultured murine endothelial cells (F-2 cells), and human peritoneal mesothelial cells. Invasive ability of SW1990 cells to F-2 cells was also observed. The adhesion leading to implantation of cancer cells to endothelial cells were inhibited by treatment with the antibodies against s-Le(a) and against beta1 integrin, respectively. Treatments with the antibodies against s-Le(a) and beta1 integrin each inhibited the development of liver metastasis in nude mice with SW1990 cells. The adhesion of SW1990 cells to peritoneal mesothelial cells was markedly inhibited by antibodies each against CD44 or beta1 integrin, but was completely blocked by using a combination of these two antibodies. These antibodies inhibited the dissemination of SW1990 cells in the peritoneal cavity of nude mice and prolonged their survival.. These findings suggest that s-Le(a) and integrin mediate the process from adhesion to implantation of SW1990 cells to endothelial cells, and CD44 and integrin play important roles in the initial attachment of SW1990 cells to mesothelial cells. It is thus speculated that compounds that interfere with the function of cell adhesion molecules may decrease the incidence of pancreatic cancer metastasis.

Topics: Animals; Antibodies; Cell Adhesion Molecules; E-Selectin; Humans; Hyaluronan Receptors; Integrin beta1; Interleukin-1; Lewis X Antigen; Liver Neoplasms; Male; Mice; Mice, Nude; Neoplasm Transplantation; Pancreatic Neoplasms; Peritoneal Neoplasms; Tumor Cells, Cultured

Human pancreatic cancer is characterized by an alteration in fucose-containing surface blood group antigens such as H antigen, Lewis b, Lewis y, and sialyl-Lewis. These carbohydrate determinants can be synthesized by sequential action of alpha(2,3) sialyltransferases or alpha(1,2) fucosyltransferases (Fuc-T) and alpha(1,3/1,4) fucosyltransferases on (poly)N-acetyllactosamine chains. Therefore, the expression and the function of seven fucosyltransferases were investigated in normal and cancer pancreatic tissues and in four pancreatic carcinoma cell lines. Transcripts of FUT1, FUT2, FUT3, FUT4, FUT5, and FUT7 were detected by RT-PCR in carcinoma cell lines as well as in normal and tumoral tissues. Interestingly, the FUT6 message was only detected in tumoral tissues. Analysis of the acceptor substrate specificity for fucosyltransferases indicated that alpha(1,2) Fuc-T, alpha(1,3) Fuc-T, and alpha(1,4) Fuc-T were expressed in microsome preparations of all tissues as demonstrated by fucose incorporation into phenyl beta-d-galactoside, 2'-fucosyllactose, N-acetyllactosamine, 3'-sialyl-N-acetyllactosamine, and lacto-N-biose. However, these fucosyltransferase activities varied between tissues. A substantial decrease of alpha(1,2) Fuc-T activity was observed in tumoral tissues and cell lines compared to normal tissues. Conversely, the activity of alpha(1,4) Fuc-T, which generates Lewis a and sialyl-Lewis a structures, and that of alpha(1,3) Fuc-T, able to generate a lactodifucotetraose structure, were very important in SOJ-6 and BxPC-3 cell lines. These increases correlated with an enhanced expression of Lewis a, sialyl-Lewis a, and Lewis y on the cell surface. The activity of alpha(1,3) Fuc-T, which participates in the synthesis of the sialyl-Lewis x structure, was not significantly modified in cell lines compared to normal tissues. However, the sialyl-Lewis x antigen was expressed preferentially on the surface of SOJ-6 and BxPC-3 cell lines but was not detected on Panc-1 and MiaPaca-2 cell lines suggesting that several alpha(1,3) Fuc-T might be involved in sialyl-Lewis x synthesis.

Topics: Aged; Carbohydrates; Epitopes; Female; Fucosyltransferases; Gene Expression; Humans; Isoenzymes; Lewis X Antigen; Male; Middle Aged; Oligosaccharides; Pancreas; Pancreatic Neoplasms; RNA, Messenger; Sialyl Lewis X Antigen; Tumor Cells, Cultured

Epitope analysis of SPan-1 and DUPAN-2 was compared with that of CA19-9 using the synthesized glycoconjugate sialyllacto-N-fucopentaose II (SLF II, sialyl-Lewis(a)) and its precursor, sialyllact-N-tetraose (LSTa, sialyl-Lewis(c)), conjugated to human serum albumin. The CA19-9 and DUPAN-2 assay systems specifically recognized SLF II and LSTa, respectively. The SPan-1 assay system recognized both SLF II and LSTa, although the reactivity with the former was far stronger than that with the latter. These results were, in general, compatible with those obtained from assaying these markers in the sera of two pancreatic cancer patients with definite Lewis-negative phenotype and in the sera of 39 CA19-9-negative pancreatic cancer patients. In conclusion, DUPAN-2 is the precursor of CA19-9 and is accumulated in the sera of pancreatic cancer patients with Lewis-negative phenotype and SPan-1 has an advantage over CA19-9 in the diagnosis of patients with Lewis-negative phenotype, although both markers have almost the same sensitivity for this malignancy.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Biomarkers, Tumor; CA-19-9 Antigen; Carbohydrate Sequence; Epitopes; Glycoconjugates; Humans; Immunohistochemistry; Lewis X Antigen; Molecular Sequence Data; Pancreatic Neoplasms; Phenotype

The diagnostic significance of measuring sialylated stage-specific embryonic antigen-1 (SLX) in pure pancreatic juice was evaluated in 20 patients with pancreatic cancer, 43 with chronic pancreatitis, 13 with cholecystolithiasis, and 15 control individuals. Four fractions of pure pancreatic juice were collected sequentially from the pancreatic duct by endoscopic cannulation. The SLX levels in all four fractions of pure pancreatic juice were significantly higher in patients with pancreatic cancer than in controls. On the other hand, patients with chronic pancreatitis or cholecystolithiasis did not have SLX levels that significantly differed from those of controls in any fraction. When the cut-off value was set as the mean concentration +2 times the standard deviation of the control values, the positive rates of SLX in the first fraction (washout phase) and the third fraction (secretory phase) of pure pancreatic juice from pancreatic cancer were 55% (11/20) and 40% (8/20), respectively. Although the false positive rates in the first fraction were high in chronic pancreatitis (30%) and cholecystolithiasis (31%), such high SLX levels in the third fraction were found only in one (2%) patient with chronic pancreatitis and in one (8%) with cholecystolithiasis. The specificities of the test for pancreatic cancer in the first fraction and the third fraction were 70% (39/56) and 96% (54/56), respectively. These results indicate that the measurement of SLX in the third fraction of pure pancreatic juice is useful as a specific marker for pancreatic cancer.

Topics: Chronic Disease; Humans; Lewis X Antigen; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis

Monoclonal antibody AM-3 (MAb AM-3) raised against a sialomucin from human colorectal carcinoma has previously been shown to define a carbohydrate epitope, which is detectable by immunocytochemistry on all investigated colonic carcinomas and is expressed in correlation with the grade of dysplasia in colonic adenomas (Hanski et al., J. Clin. Pathol., 43: 379-385, 1990). Epitope analyses in solid-phase enzyme immunoassays revealed that AM-3 antibody recognizes the sialylated Lewis(x) sequence on a branched O-linked glycan and its reductively cleaved alditol from human amniotic mucins. In comparative binding and binding inhibition studies MAbs AM-3 and CSLEX1 displayed reciprocal affinities to mucins versus gangliosides. Correspondingly, the weaker binding activities of AM-3 versus CSLEX to III3-alpha Fuc-IV3-alpha NeuAc-nLcOse4-Cer or to monogangliosides from human granulocytes were measured. Gangliosides from a human colon carcinoma were recognized by MAb CSLEX1 exhibiting a broader specificity to various sialyl-Lewis(x) antigens and by MAb FH6 reactive to sialyl-dimeric Lewis(x) antigen, but not by MAb AM-3. In conclusion, MAb AM-3 is distinguished from other sialyl Lewis(x)-specific MAbs by its selective reactivity to mucin-carried epitopes on the monomeric antigen.

Topics: Adenoma; Animals; Antibodies, Monoclonal; Biomarkers, Tumor; Birds; Carbohydrate Sequence; Cattle; Colon; Colonic Neoplasms; Female; Humans; Lewis X Antigen; Milk, Human; Molecular Sequence Data; Mucins; Oligosaccharides; Pancreatic Neoplasms; Precancerous Conditions; Sheep

We have previously described the purification and partial characterization of a new pancreatic cancer-associated antigen, a pancreatic cancer-associated mucin expressing CA19-9, CA50, Span-1, sialyl SSEA-1, and Dupan-2. This study describes the clinical evaluation of various assay systems for this antigen which depend on measuring respective serum levels. Elevated levels of antigen were detected in the sera from both patients with malignant and non-malignant diseases. However, elevated serum levels of CA19-9 and Lewisa and Lewisb epitopes on moieties were restricted to pancreatic and biliary tract cancers, although adequate sensitivity was not attained. Coordinate evaluation of these three markers improved the sensitivity to some extent without loss of specificity for the diagnosis of pancreatic and biliary tract cancers, because of the heterogeneity of the coexpression of these epitopes. We developed additional assay systems with a combination of this antigen and two lectins (Bauhinia purpurea (BPA) and Vicia villosa (VVA)). Elevated levels of BPA- and VVA-reactive antigens were detected in 41% and 31%, respectively, of pancreatic cancer sera samples. Few patients with chronic pancreatitis had an elevated serum level of either antigen, and higher elevated levels of these markers were restricted to the sera of patients with malignancies. Our results suggest that this antigen is found in the sera of patients with various conditions and in the sera of normal subjects but that antigens bearing CA19-9 or Lewisa or Lewisb epitopes and an altered carbohydrate structure recognized by BPA and VVA lectins are preferentially present in the sera of patients with pancreatic and other malignancies.

Topics: Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Chromatography, Affinity; Humans; Immunoenzyme Techniques; Lewis X Antigen; Mucins; Pancreatic Neoplasms; Sensitivity and Specificity

The Lewisx epitope (Gal beta 1-4[Fuc alpha 1-3]GlcNAc-R) can be detected in most ductal pancreatic carcinomas. However, few data pertain to its expression in normal exocrine pancreas and its biochemistry. We compared the expression of the Lewisx epitope in normal pancreas with its expression in pancreatic adenocarcinomas and tumor cell lines and to further characterize the nature of the antigens bearing this epitope with immunochemical methods. On frozen tissue sections of normal pancreas, the Lewisx epitope was detected focally in acinar cell granules; sialosyl-Lewisx was detected in centroacinar cells and the cytoplasm of intralobular ducts. Sixteen of 19 pancreatic carcinomas expressed the Lewisx antigen on tissue sections; however, there was no correlation with prognostic parameters, such as tumor grade or stage. Eighteen of 19 tumor specimens were positive for sialosyl-Lewisx. Analysis of pancreatic carcinoma cell lines (CAPAN-1, CAPAN-2, and DAN-G) revealed intracytoplasmic expression of sialosyl-Lewisx epitopes in these cells, and cell surface reactivity was detected on flow cytometry for sialosyl-Lewisx. Lectin-affinity chromatography of cytoplasmac preparations showed that Lewisx-positive antigens of normal human pancreas bind to SBA and UEA-I lectins but have little or no affinity to WGA, GS-I, or DBA lectins, indicating the presence of Fuc and Gal oligosaccharide residues. It was concluded that the Lewisx and sialosyl-Lewisx antigens are nonpolymorphic carbohydrate determinants that are present in secretory granules of acinar cells, ductules, and pancreatic secretions. This makes the Lewisx antigen suitable for the analysis of the secretory process in the exocrine pancreas and the study of secretory differentiation antigens in ductal pancreatic carcinoma.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Blotting, Western; Carbohydrate Sequence; Enzyme-Linked Immunosorbent Assay; Epitopes; Flow Cytometry; Glycoproteins; Humans; Lewis X Antigen; Molecular Sequence Data; Pancreas; Pancreatic Neoplasms; Tumor Cells, Cultured

Using sera from patients with pancreatic cancer and chronic pancreatitis, we measured the level of the adenocarcinoma-associated antigen MUSE 11. A comparative study between levels of MUSE 11 and levels of sialyl SSEA-1 antigen (SLX) was also carried out. With respect to the MUSE 11 antigen, positive incidence was found in 17 out of 26 pancreatic cancer patients (65%), and in 1 out of 13 chronic pancreatitis patients (8%). Similar results were obtained from the assay of SLX levels. However, no correlation was found between the two markers. Out of 9 samples which showed MUSE 11 negative, three were positive for SLX. Out of 13 samples showing SLX negative, seven were positive for MUSE 11. Twenty out of 26 (77%) cases showed positive results for either antigen. These data suggest that the MUSE 11 antigen may be useful for the diagnosis of pancreatic cancers.

Topics: Adult; Antigens, Neoplasm; Biomarkers, Tumor; Female; Humans; Lewis X Antigen; Male; Pancreatic Neoplasms

The expression of six sialylated carbohydrate antigens (CA19-9, CA-50, SLEX, SLX, DU-PAN-2, ST-439) was examined in malignant and nonmalignant pancreatic tissues using an immunohistochemical method to elucidate the characteristics of these carbohydrate antigens as tumor markers. All carbohydrate antigens except for sialyl SSEA-1 (SLX, 52.4%) were expressed in more than 80% of the pancreatic cancer. CA19-9 and CA-50, belonging to type I blood group antigens, and DU-PAN-2 and ST-439 were localized predominantly in the cytoplasm of cancer cells, while sialyl Lex (SLEX) and SLX, belonging to type II blood group antigens, were stained mainly on the apical membranes of malignant glands. Although type I antigens were expressed in most nonmalignant pancreatic tissues, the type II antigens and ST-439 were absent in almost all of the normal tissues and faintly expressed in few chronic pancreatitis tissues, suggesting the high tumor specificity of these antigens. Each antigen was expressed on the apical surface of ducts in normal pancreas. However, in about 30% of chronic pancreatitis cases, type I antigens and DU-PAN-2 were observed in the cytoplasm of ductal cells. All patients showing stromal stain, possibly caused by loss of antigen polar expression and shedding into the surrounding stroma adjacent to malignant glands, revealed high levels of serum antigen. This finding suggests that the stromal appearance of antigens is a significant factor in the elevation of serum antigen levels.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Humans; Immunohistochemistry; Lewis X Antigen; Pancreas; Pancreatic Neoplasms

Forty cases of carcinomas in the pancreatoduodenal region (carcinoma of the ampulla of Vater: 11 cases, carcinoma of the pancreas head (CPH): 12 cases, carcinoma of the inferior common bile duct (CIBD): 17 cases) and its non-malignant counterparts were examined immunohistochemically, using monoclonal antibodies against four Lewis (Le) blood group-related antigens and sialyl Tn antigen. TKH-2 (anti-sialyl Tn) reactivity, which is almost negative in non-malignant counterparts except for goblet cells in the duodenum, is highly positive in carcinomas, therefore, sialyl Tn antigen can be an excellent tumor marker in this region. Lex and sialyl Lex-i antigens have been regarded as pancreatic cancer-associated antigens, however, this study suggests that Lex and sialyl Lex-i are more useful markers for CIBD than CPH. Above findings imply that altered regulation of glycosyltransferase activity is associated in malignant state of the pancreas and inferior common bile duct.

Topics: Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Duodenal Neoplasms; Duodenum; Humans; Immunohistochemistry; Lewis Blood Group Antigens; Lewis X Antigen; Pancreas; Pancreatic Neoplasms

Topics: Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Diagnosis, Differential; Glycoproteins; Humans; Immunoenzyme Techniques; Lewis X Antigen; Pancreatic Neoplasms; Radioimmunoassay

A new antigen associated with pancreatic cancer was prepared by immunoaffinity chromatography using Fab'-Sepharose beads. This antigen was a glycoprotein of large molecular weight (Mr greater than 8,000,000) in its native state, estimated by size exclusion chromatography on Sephacryl S400. After sodium dodecyl sulfate-polyacrylamide gel electrophoresis and blotting analysis, several cancer-associated glycoconjugates, including CA19-9, CA50, Span-1, Dupan-2, and sialyl SSEA-1, were detected on the antigenic moiety of Mr 90,000. By an enzyme immunoassay for the antigen, elevated levels were found in pooled sera obtained from patients with various malignant and non-malignant diseases and normal subjects. However, the enhanced expression of CA19-9, Lewisa, or Lewisb epitope on the antigen molecule was restricted to the pooled sera from patients with pancreatic cancer. Furthermore, antigens from pancreatic or gastric cancer expressed ligands with intense and specific reactivity for Bauhinia purpurea (BPA), peanut (PNA), and Vicia villosa (VVA) lectins. The present assay system of the antigen, using both monoclonal antibodies (CA19-9, Lewisa, and Lewisb) and lectins (BPA, VVA and PNA), will provide a useful approach to the diagnosis of pancreatic cancer.

Topics: Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Chromatography, Affinity; Humans; Immunoenzyme Techniques; Lewis X Antigen; Ligands; Molecular Weight; Mucins; Pancreatic Neoplasms; Predictive Value of Tests

The asialocarbohydrate antigen YH206 is expressed on adenocarcinoma-associated mucin molecules which lack epitopes of CA19-9 and DU-PAN-2. To further characterize this molecule, the monoclonal antibody BM2 against the affinity-purified antigen YH206 was established. It was demonstrated by an inhibition test that antigen BM2 was an X-hapten-like structure, one of the representative oncodevelopmental antigens. Although the sensitivity of antigen BM2 in sera of stomach and pancreas cancer patients did not appear to be superior to that of antigen YH206, both antigens were complementary to each other resulting in the improvement of sensitivity. Interestingly, double-determinant enzyme immunoassays showed that antigen BM2 and YH206, both having a cryptic nature for neuraminidase, were co-expressed on the same mucin molecule in sera of patients with stomach cancer or liver cirrhosis. These data suggest that mucin molecules in serum might be classified into several groups based on the distribution of tumor-associated epitopes.

Topics: Adenocarcinoma; Animals; Antibodies, Monoclonal; Antigens, Tumor-Associated, Carbohydrate; Electrophoresis, Polyacrylamide Gel; Epitopes; Humans; Immunoblotting; Immunoenzyme Techniques; Lewis X Antigen; Mice; Mucins; Pancreatic Neoplasms; Stomach Neoplasms

Expression of blood group-related antigens and the binding pattern of Ulex europaeus-I (UEA-I) in fetal and newborn hamster pancreases was examined immunohistochemically by monoclonal antibodies (MoAbs) against blood group antigens and by peroxidase-conjugated UEA-I. The fetal hamster pancreas was detected histologically at the 12th day of gestation. MoAbs A, B and Le(a) were not immunoreactive with pancreatic cells in any stage of development nor were they after birth. Le(x) was first expressed in the luminal surface of duct cells at the 13th day of gestation, disappeared at the 15th day of gestation, was re-expressed after birth in acinar cells and was absent in the adult pancreas. Le(b) and Le(y) were expressed in acinar cells in late fetal and early newborn stages, but disappeared with maturation and were absent in the adult pancreas. UEA-I binding, however, was demonstrated in both fetal and adult pancreatic tissue. In cancer cells induced by BOP, blood group antigens except for Le(a) and UEA-I binding were found in various reactivity. These findings suggest that in hamsters (i) A and B antigens are tumor-related antigens; (ii) H, Le(b), Le(x) and Le(y) are oncofetal antigens; and (iii) fucosylation is an important event in cell differentiation.

Topics: ABO Blood-Group System; Animals; Antibodies, Monoclonal; Blood Group Antigens; Cricetinae; Female; Glycolipids; Immunoenzyme Techniques; Isoantigens; Lectins; Lewis X Antigen; Male; Mesocricetus; Pancreas; Pancreatic Neoplasms; Plant Lectins

Topics: Biomarkers, Tumor; Female; Glycolipids; Humans; Immunoradiometric Assay; Lewis X Antigen; Lung Neoplasms; Male; Ovarian Neoplasms; Pancreatic Neoplasms; Specimen Handling

In order to evaluate the usefulness of sialyl SSEA-1 (SLX) as a tumor marker of digestive cancers, serum levels of the antigen were determined in 334 patients with malignancies and 196 patients with benign diseases. The results indicated that positivity of the antigen in sera from malignant patients was highest in pancreatic cancer (58%) and biliary tract cancer (56%). False positive incidence of SLX in sera from benign diseases was as low as 6%, revealing low false positivity. Comparison with other tumor markers such as CA19-9, CA-50, CEA and ST-439 showed that positivity of SLX was as high as that of CEA, whereas it was lower than that of CA19-9 or CA-50. On the other hand, false positivity of SLX as well as ST-439 was lowest, and accuracy of SLX was no less high than that of CA19-9 or CA-50. In sera of pancreatic and biliary tract cancer, positive incidences of CA19-9, CEA and ST-439 were 80%, 64% and 53%, respectively, and the diagnostic efficiency increased by combined assay of SLX with CA19-9 (88%), CEA (81%) and ST-439 (71%). SLX appears to be no less useful than the other recently developed carbohydrate antigens or CEA as serum tumor marker for pancreatico-biliary cancer.

Topics: Biliary Tract Neoplasms; Biomarkers, Tumor; Glycolipids; Humans; Lewis X Antigen; Pancreatic Neoplasms; Predictive Value of Tests