lewis-x-antigen and Adenoma

To discover and confirm blood-based colon cancer early-detection markers.. We created a high-density antibody microarray to detect differences in protein levels in plasma from individuals diagnosed with colon cancer <3 years after blood was drawn (ie, prediagnostic) and cancer-free, matched controls. Potential markers were tested on plasma samples from people diagnosed with adenoma or cancer, compared with controls. Components of an optimal 5-marker panel were tested via immunoblotting using a third sample set, Luminex assay in a large fourth sample set and immunohistochemistry (IHC) on tissue microarrays.. In the prediagnostic samples, we found 78 significantly (t-test) increased proteins, 32 of which were confirmed in the diagnostic samples. From these 32, optimal 4-marker panels of BAG family molecular chaperone regulator 4 (BAG4), interleukin-6 receptor subunit beta (IL6ST), von Willebrand factor (VWF) and CD44 or epidermal growth factor receptor (EGFR) were established. Each panel member and the panels also showed increases in the diagnostic adenoma and cancer samples in independent third and fourth sample sets via immunoblot and Luminex, respectively. IHC results showed increased levels of BAG4, IL6ST and CD44 in adenoma and cancer tissues. Inclusion of EGFR and CD44 sialyl Lewis-A and Lewis-X content increased the panel performance. The protein/glycoprotein panel was statistically significantly higher in colon cancer samples, characterised by a range of area under the curves from 0.90 (95% CI 0.82 to 0.98) to 0.86 (95% CI 0.83 to 0.88), for the larger second and fourth sets, respectively.. A panel including BAG4, IL6ST, VWF, EGFR and CD44 protein/glycomics performed well for detection of early stages of colon cancer and should be further examined in larger studies.

Topics: Adaptor Proteins, Signal Transducing; Adenoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; CA-19-9 Antigen; Case-Control Studies; Colonic Neoplasms; Cytokine Receptor gp130; Early Detection of Cancer; ErbB Receptors; Female; Humans; Hyaluronan Receptors; Lewis X Antigen; Male; Middle Aged; Oligosaccharides; Protein Array Analysis; von Willebrand Factor

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Animals; Biomarkers, Tumor; Brain; Female; Flow Cytometry; Gene Expression Profiling; Humans; Immunohistochemistry; Lewis X Antigen; Male; Mice, Inbred NOD; Mice, SCID; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Transplantation; Neoplastic Stem Cells; Pituitary Neoplasms; Real-Time Polymerase Chain Reaction; Single-Cell Analysis

The role of interleukin-17 (IL-17) in the tumor microenvironment is controversial. We analyzed the in situ tumor expression of IL-17 in colorectal cancer (CRC), adenoma and non-tumor tissue to explore the possible correlation of IL-17 expression to clinicopathological characteristics, tumor-infiltrating neutrophils (TINs) and survival in CRC.. We reviewed the records of 78 consecutive patients diagnosed with CRC. Archival tissues were used. Thirty-six patients with colorectal adenoma were also included. From the 78 CRC patients, we randomly chose 40 cases and collected non-tumor tissue at 10 cm from the edge of the resected tumor. Immunohistochemistry was performed using anti-IL-17 and anti-CD15 (targeting neutrophils) antibody, respectively. Real-time PCR was used to detect IL-17 mRNA in different tissues. Associations between IL-17 expression, clinicopathological parameters and prognosis were evaluated.. The level of IL-17 mRNA was higher in CRC than in adenoma and non-tumor tissue (P < 0.05). Positive IL-17 protein expression was observed more frequently in CRC as compared to colorectal adenoma and non-tumor tissue, respectively (P < 0.01). IL-17 expression correlated to well differentiation and early stage CRC. The number of CD15+ neutrophils significantly increased in CRC and positively correlated to the expression of IL-17 (P < 0.05). Both Kaplan–Meier analysis and multivariate Cox regression analysis indicated that patients with positive IL-17 expression showed better overall survival.. The association between IL-17 expression and the clinicopathological parameters, as well as the clinical outcome suggests a significant role of IL-17 in CRC. IL-17 is a marker of favorable prognosis.

Topics: Adenoma; Aged; Biomarkers, Tumor; Colorectal Neoplasms; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Interleukin-17; Kaplan-Meier Estimate; Lewis X Antigen; Male; Middle Aged; Neutrophils; Prognosis; Proportional Hazards Models; Real-Time Polymerase Chain Reaction; Treatment Outcome; Tumor Microenvironment

Overlapping morphologic patterns that may be observed in goiter, follicular adenoma, and papillary carcinoma can limit the cytologic evaluation of the thyroid gland. In an attempt to develop a useful adjunctive test, the immunocytochemical reactivity of HBME-1, carcinoma antigen 19-9 (CA 19-9), and CD-15 (Leu-M1) was tested on 59 cell block preparations from fine-needle aspirations of the thyroid gland. HBME-1 monoclonal antibody was reactive in all 21 papillary carcinomas, in 4 of 18 adenomas, and in 5 of 20 goiters. CA 19-9 was identified in 13 of 21 carcinomas, 1 goiter, but none of the adenomas. CD-15 was present in 15 of 21 carcinomas, 1 goiter, and 1 adenoma. We conclude that HBME-1 is a sensitive marker of papillary thyroid carcinoma. CD-15 and CA 19-9 are less sensitive but more specific. This panel can be useful to help classify morphologically equivocal lesions. As with all immunocytochemical testing, caution must be exercised in the interpretation of results, and correlation made with morphologic and clinical data.

Topics: Adenoma; Antibodies, Monoclonal; Antigens, Neoplasm; Biopsy, Needle; CA-19-9 Antigen; Carcinoma, Papillary; Diagnosis, Differential; Goiter, Nodular; Humans; Immunohistochemistry; Lewis X Antigen; Sensitivity and Specificity; Thyroid Neoplasms; Thyroid Nodule

Pokeweed mitogen (PWM) lectin, known to bind branched poly-N-acetyllactosamines, has a highly selective affinity for human colorectal carcinomas. We performed light microscopic (LM) histochemistry with PWM lectin on paraffin sections of human colorectal tissues. In histological sections, normal mucosae and adenomas with mild dysplasia exhibited negative reaction (0/10, 0/13, respectively) with or without neuraminidase pre-digestion, whereas adenomas with moderate dysplasia showed a small increase in PWM lectin reactivity after neuraminidase digestion (4/23). In contrast, we observed a high incidence of positive reactivity in colorectal carcinoma without neuraminidase pre-digestion (38/44). After digestion with neuraminidase, there was increased reactivity of colorectal carcinomas in situ (7/12) and invasive carcinomas (13/32). These results imply that human colorectal carcinomas consistently contain substantial amounts of PWM-reactive branched poly-N-acetyllactosamine glycoconjugates structures. We also compared the staining patterns of PWM lectin and monoclonal antibodies (MAb) directed to Lewis X (LeX) or Lewis Y (LeY) antigen. PWM lectin reactivity was largely confined to the apical membranes of carcinoma tissues. MAb-LeX or MAb-LeY immunoreactivity was seen on the apical membranes and in the cytoplasm of both adenomas and carcinomas. Therefore, histochemical studies with this lectin should be useful for identification of carcinoma tissues and analysis of glycoconjugates associated with colorectal carcinoma.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Carcinoma in Situ; Colorectal Neoplasms; Female; Glycoconjugates; Histocytochemistry; Humans; Immunohistochemistry; Intestinal Mucosa; Lewis X Antigen; Male; Middle Aged; Pokeweed Mitogens

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

Alterations of carbohydrate chain antigens were investigated immunohistochemical in relation to histological malignant changes on 62 cases of gastric atypical epithelial lesions (adenomas) which were diagnosed as Group-III at the first biopsy and then followed up more than one year. Among 7 carbohydrate chain antigens which are related to Lewis antigens, sialyl Lex-i antigen showed the most impressive findings; The positivity percentage of the first biopsy specimens of Group-III was 6%, however, it raised to 33% in the final biopsy specimens of Group-IV, 50% in the resected specimens of border-line lesions, and 67% in the resected specimens of carcinomas. The results indicate that there exists a close correlation between malignant change of gastric atypical epithelial lesions and alteration of carbohydrate chain in terms of sialylation.

Topics: Adenoma; Aged; Aged, 80 and over; Antigens, Tumor-Associated, Carbohydrate; Carcinoma; Female; Follow-Up Studies; Gastric Mucosa; Humans; Hyperplasia; Immunohistochemistry; Lewis X Antigen; Male; Middle Aged; Stomach Neoplasms

This study was undertaken to determine the value of SLX and CA19-9 in the tissue and serum in colorectal cancer and adenoma including the relation to Lewis blood type. SLX isolated by Hakomori et al is one of sialyl SSEA-1 antigens characterized by type 2 chain lacto series glycolipids. Distribution of SLX and CA19-9 was determined in 137 specimens of colorectal cancer (107 advanced and 30 early cancer) and 20 specimens of adenoma by using immunoperoxidase (ABC) method. Serum SLX, CA19-9 and CEA levels were measured preoperatively in 58 cases with histologically proven colorectal cancer by using RIA kits. Simultaneously, Lewis blood type were determined by hemagglutination test in 31 cases. The following results were obtained; 1) SLX and CA19-9 were mostly observed in apical membrane and luminal contents, but a few in cytoplasma of cancer tissue. Positive rate of SLX and CA19-9 was 96.2% and 88.8%, respectively. 2) SLX and CA19-9 were lightly stained in the goblet cells and surface epithelium in some of the mucosa adjacent to the cancer tissue, and positive rate of SLX and CA19-9 was 24.3% and 32.7%, respectively. 3) Positive rate of SLX and CA19-9 was 60% and 50% in adenoma, and 94% and 80% in "m" cancer. Positive rate was not different due to grade of dysplasia of adenoma, but distribution of SLX or grade of the staining of CA19-9 was different between adenoma with mild and moderate dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Adenoma; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Colorectal Neoplasms; Glycolipids; Humans; Immunohistochemistry; Lewis Blood Group Antigens; Lewis X Antigen

The monoclonal antibody Hy2D4 was found to label a previously undescribed subset of rat and human anterior pituitary cells. The antibody binding site appears to be a carbohydrate moiety previously named "X hapten." Double-label immunofluorescence studies in both normal rat and postmortem human pituitaries showed that this antigen is distributed on a subset of adrenocorticotropic hormone (ACTH)-positive cells, but is not detectable in cells immunoreactive for growth hormone, prolactin (PRL), thyroid-stimulating hormone, or luteinizing hormone. Since X hapten labeling revealed a biological subdivision of corticotroph cells, it was expected that some ACTH-positive tumors would be immunoreactive, but that tumors of other hormonal types would be negative. Instead, in 21 surgical specimens examined, tumors of all hormonal types were found to show immunoreactivity. To determine whether experimental proliferative changes in the pituitary could explain the shift in the cell type expressing the antigen, PRL-cell hyperplasia was induced in rats through chronic (8-week) exposure to diethylstilbestrol. The fraction of X-positive cells increased in these hyperplastic glands almost ninefold and, as in human adenomas, many non-corticotroph cells expressed the X marker in this model. However, the non-corticotroph cells expressing X were predominantly growth hormone cells, not the proliferative PRL cells. Thus, expression of the antigen does not necessarily imply that a cell is in a proliferative mode. While it is not known what role an altered expression of this antigen might play, the antibody offers a probe into cellular biology of human and experimental pituitary tumors.

Topics: Adenoma; Adrenocorticotropic Hormone; Animals; Antigens, Neoplasm; Cells; Diethylstilbestrol; Epitopes; Glycolipids; Humans; Hyperplasia; Immunochemistry; Lewis X Antigen; Pituitary Gland; Pituitary Gland, Anterior; Pituitary Neoplasms; Prolactin; Rats

The expression of carbohydrate antigen 19-9 (CA 19-9) and stage-specific embryonic antigen 1 (SSEA-1) in various human colorectal epithelia was examined by an immunohistochemical method. In mucosa remote from the carcinoma, CA 19-9 was not expressed, whereas SSEA-1 was only faintly expressed in lower crypts in all cases. In mucosa adjacent to the carcinoma, CA 19-9 was weakly expressed in upper crypts in 20% of the cases, whereas SSEA-1 was expressed not only in lower crypts in all cases but also in upper crypts in 93.3% of the cases. In adenoma, CA 19-9 was expressed in 80.6% of the cases, and SSEA-1 was expressed in all cases. The expression of both antigens was to some extent related to the degree of cellular atypia. In focal carcinoma in adenoma, CA 19-9 was strongly and diffusely expressed in 50% of the cases, and SSEA-1 was strongly and diffusely expressed in all cases. In advanced carcinoma, CA 19-9 was homogeneously or heterogeneously expressed in 82.2% of the cases, and SSEA-1 was homogeneously or heterogeneously expressed in all cases, but lower intensity of SSEA-1 staining was associated with a decrease in the degree of carcinoma differentiation. These results show that the expression of both CA 19-9 and SSEA-1 changes along with neoplastic transformation and progression in the colon and rectum. Immunohistochemical studies of SSEA-1 in flat colorectal mucosa might be a useful approach for detecting foci with preneoplastic change in the general population, whereas those of SSEA-1 and CA 19-9 could be a useful method for detecting focal carcinoma in adenoma.

Topics: Adenoma; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Carcinoma; Colon; Colonic Neoplasms; Glycolipids; Humans; Intestinal Mucosa; Lewis X Antigen; Rectal Neoplasms; Rectum