alpha-Neup5Ac-(2--3)-beta-D-Galp-(1--4)-[alpha-L-Fucp-(1--3)]-D-GlcpNAc and Carcinoma--Ductal--Breast

To investigate the possible roles of E-selectin and its ligand, Sialyl Lewis X, in lymph node metastasis of invasive micropapillary carcinoma of the breast, 100 cases of invasive micropapillary carcinoma and 97 cases of invasive ductal carcinoma were analyzed immunohistochemically for the expression of E-selectin and Sialyl Lewis X, along with CD34, to measure the microvessel density of invasive micropapillary carcinoma. We found that the number of E-selectin-positive vessels was greater in invasive micropapillary carcinoma than in invasive ductal carcinoma, and it was significantly correlated with the histological grade, the number of positive lymph nodes, and the microvessel density of invasive micropapillary carcinoma. The Sialyl Lewis X expression of invasive micropapillary carcinoma was higher than that of invasive ductal carcinoma, which was also associated with lymph node metastasis. In invasive micropapillary carcinoma, the Sialyl Lewis X expression was predominantly in the stroma-facing surface of the cell clusters and the adjacent stroma, while in invasive ductal carcinoma it was largely intracytoplasmic or intercellular. These findings suggested that E-selectin and Sialyl Lewis X might play an important role in lymph node metastasis in invasive micropapillary carcinoma. The expression pattern of Sialyl Lewis X in invasive micropapillary carcinoma suggested that the reversal of cell polarity of invasive micropapillary carcinoma might be as an important factor for the morphogenesis and possibly the pathogenesis, especially their higher rates of lymph node metastasis.

Topics: Adenocarcinoma, Papillary; Biomarkers, Tumor; Breast Neoplasms; Carcinoma, Ductal, Breast; Cell Polarity; E-Selectin; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Microvessels; Neoplasm Invasiveness; Oligosaccharides; Sialyl Lewis X Antigen

One of the most urgent requirements in breast cancer is the development of a blood-based test for early detection and prognosis. Previously published results found a significant difference between specific glycan levels in patients with advanced breast cancer and healthy controls. The aim of this investigation was to address a more clinically relevant problem, i.e., whether the measurement of specific glycans could identify women with aggressive disease at an early stage. In order to reduce potential bias in this study, blood samples from patients were collected, stored and analyzed in a similar manner. Agalactosyl biantennary glycans (FA2) and glycans containing the sialyl Lewis x epitope (A3F1G1 and A2F1G1) were measured using high throughput normal-phase high-performance liquid chromatography in combination with exoglycosidase digestions in sera from 52 patients with early breast cancer (21 with lymph node-negative and 20 with lymph node-positive disease) and 134 women with benign breast disease. The combined levels of the glycans were significantly higher in patients with lymph node metastases compared to women without these metastases. Lymph node status is the single most important determinant of survival in early stage breast cancer. As high levels of these glycans were associated with nodal metastases, their measurement may provide a new non-invasive approach to determining prognosis in women with newly diagnosed breast cancer.

Topics: Adenocarcinoma, Mucinous; Axilla; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Chromatography, High Pressure Liquid; Female; Humans; Lewis X Antigen; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Polysaccharides; Prognosis; Sialyl Lewis X Antigen

We have shown previously that the mucins of the human pancreatic cancer cell line, SW1990, have both sialyl-Lewis(a) and sialyl-Lewis(x) carbohydrate ligands that are implicated in tumor cell metastasis. In the present study, we undertook to identify the protein core of these mucins. SW1990 mucins that carry sialyl-Lewis(a) and sialyl-Lewis(x) bound to the MUC1 peptide-specific mAb 139H2. Removal of most of the sialic acids from SW1990 mucins by neuraminidase greatly enhanced binding of two other MUC1 peptide specific antibodies, HMFG-2 and SM-3. After removal of sialic acids, most of the mucins rich in sialyl-Lewis(a) and sialyl-Lewis(x) oligosaccharides no longer bound to a DEAE-cellulose column at pH 8.0. These results indicate that at least part of the sialyl-Lewis(a) and sialyl-Lewis(x) in SW1990 cells is associated with the MUC1 polypeptide. Moreover, sialic acids play an important role in determining the net negative charge of sialyl-Lewis(a) and sialyl-Lewis(x) rich mucins and in obscuring MUC1 peptide regions.

Topics: Amino Acid Sequence; Antibodies, Neoplasm; Antibody Specificity; Antigens, Tumor-Associated, Carbohydrate; CA-19-9 Antigen; Carcinoma, Ductal, Breast; Epitope Mapping; Gangliosides; Humans; In Vitro Techniques; Membrane Glycoproteins; Molecular Sequence Data; Mucin-1; Mucins; Neuraminidase; Pancreatic Neoplasms; Peptides; Sialyl Lewis X Antigen; Tumor Cells, Cultured