lewis-x-antigen and Carcinoma--Ductal--Breast

Fucosylated glycans synthesized by α1,3/4-fucosyltransferase (FUT3) enzyme play an important role in breast cancer prognosis and metastasis, being involved in the binding of circulating tumor cells to the endothelium and being related to tumor stage, metastatic potential and chemoresistance. Despite the pro-tumor action of this enzyme, studies have demonstrated its role in natural killer-induced cytotoxicity through the recognition of sialyl Lewis X by C-type lectin receptors and through extrinsic apoptosis pathway triggered by Apo2L-TRAIL. This study aimed to investigate the expression pattern of FUT3 in invasive breast carcinoma (IDC) from patients of Pernambuco state, Northeast of Brazil, and genotype FUT3 promoter region to identify possible SNPs that could be associated with variations in FUT3 expression. Immunohistochemistry assay was used to access the FUT3 expression in normal (n=11) and tumor tissues (n=85). DNA sequencing was performed to genotype the FUT3 promoter region in patients with IDC (n=109) and healthy controls (n=110). Our results demonstrated that the absence of FUT3 enzyme is related to breast's IDC. The non-expression of FUT3 was more frequent in larger lesions and also in HER2 negative IDC tumors. Genomic analysis showed that two variations localized in FUT3 promoter region are possibly associated with IDC. Our results suggest that minor allele T of SNP rs73920070 (-6933 C>T) confers protection whereas minor allele T of SNP rs2306969 (-6951 C>T) triggers to susceptibility to IDC in the population of Pernambuco state, Northeast of Brazil.

Topics: Brazil; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Fucosyltransferases; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Lewis X Antigen; Promoter Regions, Genetic

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

There is sufficient evidence that blood group related Lewis antigens are tumor-associated molecules. We have conducted immunohistochemical analysis of the expression of Lewis antigens in breast cancer tissue as an indicator of the degree of malignancy and as a prognostic factor. The studies were performed by examining 43 female patients diagnosed with invasive ductal carcinoma of the breast. Postoperative specimens were stained immunohistochemically using a panel of monoclonal antibodies (MAbs) specific for tumor-associated antigens: sialosyl LewisA, LewisA, LewisB, Lewisx, and LewisY. The aims of the study were to compare the appearance of metastases, degree of cancer stage (pTNM), and its histologic differentiation with the expression of Lewis phenotype. The evaluation of antigen expression was performed quantitatively and independently by two pathologists. Statistical significance was defined by Mann-Whitney test. The presented analysis of Lewis antigens showed higher expression of LeB and LeA (p = 0.03) in patients in stage N2 than in stage N1. The expression of LeB and LeY was higher in patients in stage T4 than in stage T1 (p = 0.02). No differences were observed for histologic differentiation. These data suggest that the expression of sialosyl-LeA and LeB antigens in breast cancer may predict metastases to lymph nodes.

Topics: Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Breast Neoplasms; Carcinoma, Ductal, Breast; Female; Glycosphingolipids; Humans; Immunohistochemistry; Lewis Blood Group Antigens; Lewis X Antigen; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Prognosis

The expression of the cell adhesion molecule CD15 (also known as Lewis x) by breast cancers and by adjacent normal and benign breast epithelium was investigated in a series of 98 tumours. Immunohistochemistry was performed on paraffin sections using the anti-CD15 monoclonal mouse IgM antibody Dako-M1. Some 35% of cancers expressed CD15, as did 45% of normal and 60% of hyperplasia. No association was observed between cancer cell staining, or any epithelial staining (cancer, benign and normal), and tumour size, histological grade, nodal status, age at diagnosis or the frequency of 'events' (recurrence or death). Chi-squared tests in each case were non-significant. The pattern of CD15 expression by breast cancer was frequently associated with the leading edge of invading tumour or with the outer edge of boli of carcinoma in situ, possibly suggesting a potential role in invasiveness, and with cancer cells trapped intravascularly, possibly suggesting a role in metastasis.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Female; Granulocytes; Humans; Immunohistochemistry; Lewis X Antigen; Middle Aged; Neoplasm Invasiveness