Characterization of Monoclonal Antibodies Reactive with Normal Resting, Lactating and Neoplastic Human Breast

Abstract

Mouse monoclonal antibodies reacting with human mammary gland constituents have been generated and characterized in an attempt to raise breast- or breast-cancer-specific antisera. The immunogens used in these studies included fractionated human milk fat globule membrane, the human breast cancer cell line MCF7 and a crude membrane preparation derived from an axillary nodal metastasis from a patient with breast cancer. Of the antibodies obtained, 8 were characterized and found to bind to different structures in the normal breast. The antibody LICR-LON-LC28 recognizes secretory component and binds strongly to normal resting and lactating breast, but only focally to a minority of breast carcinomas. The antibodies LICR-LON-14.1 and 32.2 react strongly with the lactating breast and recognize κ- and β-casein, respectively. Caseins are not produced by breast tumors. The antibodies LICR-LON-TW19.5, H10A and 39.8 all react with carbohydrate epitopes and bind heterogeneously to normal resting breast luminal epithelium and cellular subsets of breast carcinomas. LICR-LON-59.2 and 19.2 react with normal breast myoepithelial cells and the basement membrane, respectively. LICR-LON-59.2 is unusual as a myoepithelial marker in that it stains cells in the majority of breast carcinomas. LICR-LON-19.2 shows extensive reactivity to tumor cell lines in culture but has no reactivity with carcinoma cells from breast biopsies.

Immunocytochemical identification of cell types in benign and malignant breast diseases: variations in cell markers accompany the malignant state.

“…In our study there is a preponderance of immunocytochemical staining for keratin 18 in the majority of the benign lesions of the breast. The extent of staining, although highly variable, is usually reduced in invasive carcinoma, independent of the histological types examined.…”

“…More recently, limited studies with single immunocytochemical stains for myoepithelial (9)(10)(11)(12)(13) or secretory alveolar cells (1415) have broadly confirmed the absence of myoepithelial and secretory alveolar cells in invasive ductal and lobular carcinoma of the breast, although there have been exceptions in both instances (16)(17)(18). However, the variation in cell expression of some of the antigenic markers for either cell type with location and differentiation within the normal parenchyma of the breast, particularly those based on keratins for the myoepithelial cell (19), may have reduced the significance of immunocytochemical results based on the use of a single antigenic marker for a specific cell type.…”

The histogenesis of mammary and extramammary Paget's disease

“…H.lO.A is a mouse monoclonal antibody raised to the integral membrane protein fraction of HMFG. It does not react with EMA but recognizes a carbohydrate epitope on glycoproteins of molecular weight 53 kD and heavier (Skilton et al 1989). 4 LICR-LON-TW19 (used undiluted) was provided by Dr Martin Gore (Ludwig Institute-for Cancer Research).…”

“…4 LICR-LON-TW19 (used undiluted) was provided by Dr Martin Gore (Ludwig Institute-for Cancer Research). T W 1 9 is a mouse monoclonal antibody raised to the void fraction of a peanut lectin column after running solubilized HMFG (Skilton et al 1989). It also recognizes a carbohydrate epitope or glycoproteins of molecular weight 42 kD and above.…”

Increased spatial resolution in transillumination using collimated light

“…To increase the probability of the detection of cancers by absorption, natural markers could be used. Such markers have not been established with any certainty, although several have been proposed [31], and in one past commercial application [32] some possible markers are included in the detection of lesions.…”