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Serum and immunohistochemical studies of NCC-ST-439 in breast cancer.

It has been thought that NCC-ST-439 antigen (ST-439) is a tumor-related carbohydrate antigen. The authors conducted serum and immunohistochemical studies to investigate the clinical significance of ST-439 in breast cancer. The level of serum ST-439 was elevated in advanced and recurrent breast cancers. In comparison with CEA and CA15-3, ST-439 was superior in sensitivity but inferior in specificity to these markers. The level of serum ST-439 showed no correlation with the levels of CEA or CA15-3. In the combination assay of these three markers, 80.6% of recurrent cases and 33.8% of primary cases were positive. Immunohistochemically, the expression of ST-439 was observed in 28.1% of noncancerous mammary duct epithelium and in 38.1% of the cancerous portion. From the above, we concluded that ST-439 was a tumor-related antigen and could be a tumor marker with high sensitivity in breast cancer.

Adenofibroma↗

Myoepithelial differentiation and basal lamina deposition in fibroadenoma and adenosis of the breast.

Sixteen cases of breast fibroadenomas and 11 of adenosis were studied ultrastructurally; emphasis was placed on the patterns of myoepithelial differentiation and the number and appearance of the basal laminae. Ducts of both fibroadenomas and adenosis showed well differentiated, peripherally arranged myoepithelial elements with conspicuous cytoplasmic filaments and numerous hemidesmosomes; focal myoepithelial multilayering occurred. Myoepithelial cells exhibited complex, convoluted cytoplasmic processes extending into the stroma and resulting in the formation of pseudocysts containing stromal material. Basal lamina deposition was invariably found; basal lamina reduplication was extremely frequent. Basal lamina discontinuities with cytoplasmic processes extending directly into the stroma were seen in adenosis. Myoepithelial features and conspicuous basal lamina deposition indicate advanced differentiation and correlate well with the benign prognosis of these lesions. The focal basal lamina gaps in adenosis may be significant in the long-term evolution of this and similar dysplastic processes.

Adenofibroma↗

Transferrin receptor expression in non-malignant and malignant human breast tissue.

The expression of transferrin receptor by normal, pregnant and benign hyperplastic breast lesions and by breast carcinomas has been investigated immunohistochemically using two monoclonal antibodies directed against the receptor. Unlike a previous immunohistological study in which staining was confined to malignant breast, transferrin receptor has been detected in pregnant breast and in benign lesions as well as in all carcinomas examined. The latter showed variable reactivity but with staining of most cells in 70 per cent of cases. Although the expression of transferrin receptor in non-malignant conditions may be related to cell proliferation, as has been suggested from studies of activated cells, the extent of reactivity of carcinomas has shown no correlation with tumour characteristics such as differentiation and local tumour spread. It is therefore suggested that the immunologically active transferrin receptor of breast carcinomas may have significance other than that relating to proliferation. The finding that with some carcinomas differences in staining occurred between the two antibodies is a further illustration of the complexities of the nature of transferrin receptor.

Adenofibroma↗

Immunocytochemical demonstration and significance of p21 ras family oncogene product in benign and malignant breast disease.

It has been suggested that the immunocytochemical demonstration of the p21 ras oncogene product is a useful marker of malignancy in breast disease. We have studied the reactivity of a series of specimens of benign and malignant breast disease with the anti ras p21 monoclonal antibody Y13-259, and shown widespread positive staining in both benign and malignant (including metastatic) disease as well as in adjacent 'normal' epithelium. In addition some staining of stromal cells as well as nerve fibres was observed. Our results suggest that the presence of ras p21 protein as demonstrated by this antibody is not a useful marker of malignancy or of proliferating epithelium but is rather a normal feature of certain cell types.

Adenofibroma↗

Structural distinctions among human breast epithelial cells revealed by the monclonal antikeratin antibodies AE1 and AE3.

Two monoclonal antikeratin antibodies, AE1 and AE3, were used in indirect immunocytochemistry to examine keratin expression in normal, benign proliferative, and malignant human breast epithelium. Both antibodies reacted strongly with most luminal cells in ducts and acini of normal gland. While AE1 did not stain myoepithelium, AE3 recognized myoepithelial cells of ducts but not acini, implying a cytoskeletal difference between the myoepithelium of these two components. Moreover, the antibodies reacted differently with the myoepithelium of intracanalicular as compared with pericanalicular types of fibroadenomas. Tumour cells of infiltrating ductal carcinomas with a prominent intraductal component stained more homogeneously with AE1 and AE3 than those without intraductal growth. The results provide evidence for two phenotypes of myoepithelial cells and for the presence of cryptic keratin epitopes in human breast epithelial cells. The finding that neither AE1 nor AE3 is a universal detector of these cells has important clinical and experimental implications.

Adenofibroma↗

Lectin binding in the male breast.

Twenty-four male breast lesions including ten normal, ten gynaecomastia, and four infiltrating carcinomas were studied for the presence and distribution of lectin binding carbohydrates. For comparison, tissue sections of five normal female breast lesions, ten each of fibrocystic disease, fibroadenoma, and carcinoma, were also included in this study. Formalin-fixed, paraffin-embedded tissues were tested with Glycine maximus (SBA), Dolichos biflorus (DBA), Triticum vulgaris (WGA), Concanavalia ensiformis (Con A), Lotus tetragonolobus (LTA), Arachis hypogaea (PNA), and Bandeiraea simplicifolia (BSAI). The lectin-binding patterns were similar in normal, gynaecomastia, and carcinoma, and were not pathognomonic to any male breast lesion. These lectin reactive patterns in the male breast appear to be similar to those reported for the female breast lesions.

Adenofibroma↗

p21 ras protein expression in benign and malignant human breast.

The ras oncogenes encode for GTP binding and GTPase active proteins of relative molecular mass 21,000 (p21ras) which are involved in the transduction of stimuli for cell proliferation. There have been conflicting reports about the detection and significance of expression of p21ras protein in human breast disease as determined by immunohistochemistry. The antibody Y13-259, which detects a single protein of Mr 21,000, has been applied immunohistochemically to frozen sections of normal, benign proliferative breast, fibroadenomas, and carcinomas. Uniform staining of normal breast epithelium and myoepithelium was found, with occasional stronger staining in areas of epithelial hyperplasia in benign breast disease. Contrary to previous reports, decreased expression, usually heterogeneous, was found in half of the carcinomas examined. Thirty per cent of the carcinomas exhibited heterogeneous staining stronger than that of normal breast, interpreted as increased expression of p21ras protein. This did not relate to tumour grade or node status but showed a significant correlation with proliferation rate as determined by the monoclonal antibody Ki-67. This study confirms previous reports that p21ras protein expression is a feature of normal cells, and has identified increased expression in 30 per cent of tumours associated with higher proliferation rates, which is a lower incidence than previously claimed when a different antibody was employed.

Adenofibroma↗

Low expression of beta 1, alpha 2 and alpha 3 subunits of VLA integrins in malignant mammary tumours.

The Very Late Antigens (VLAs) are alpha beta heterodimeric transmembrane proteins mediating cell-substratum as well as cell-cell interactions. Changes in their expression and/or function seem to occur in a number of invasive carcinomas and may at least in part explain their abnormal patterns of growth and differentiation. Using monoclonal antibodies to the beta 1 (DH12, A1A-5), alpha 2 (B1.515) and alpha 3 (E1.56) chains, VLA-2 (alpha 2 beta 1) and VLA-3 (alpha 3 beta 1) were studied on cryostat sections of three fibroadenomas and 43 invasive breast carcinomas (29 ductal, 14 lobular) by the avidin-biotin complex immunoperoxidase technique. In non-neoplastic breast tissue and in fibroadenomas VLA-2 and VLA-3 were expressed by myoepithelial cells and on the basolateral surface of the luminal cells. There was weak or absent expression of alpha 2, alpha 3 and the common beta 1 chain in the majority of invasive carcinomas compared to the adjacent normal breast epithelium and preinvasive (in-situ) carcinomas. In addition, the expression of the alpha 2 chain of VLA-2 was reduced significantly (P less than 0.005) in the poorly differentiated ductal breast carcinomas (Grade III) compared to the well (Grade I) and moderately (Grade II) differentiated ductal tumours. These data give further evidence that loss or down-regulation of VLA-2 and VLA-3 occur relatively frequently in invasive cancers, and, at least in the invasive ductal breast carcinomas. Loss of an extracellular matrix receptor controlling growth and differentiation seems to be one of the abnormalities underlying the progression towards an undifferentiated morphology.

Adenofibroma↗

Co-ordinate expression of the alpha-6 integrin laminin receptor sub-unit and laminin in breast cancer.

Interactions between cells and extracellular matrices are mediated in part by a family of heterodimeric molecules known as integrins. We have investigated, using immunohistology, the distribution of six integrin alpha sub-units in normal breast tissue and 26 breast carcinomas. Alpha-1 integrin (collagen/laminin receptor sub-unit) was detected in myoepithelium, but not in luminal epithelium nor in most (20/26) carcinomas. Its expression on fibroblasts was enhanced in desmoplastic stroma. Both benign and malignant epithelium showed uniform positive staining for alpha-2 (collagen receptor sub-unit) and for alpha-3 (collagen/fibronectin/laminin receptor sub-unit). All epithelium was negative for alpha-4 (sub-unit of a fibronectin receptor). Epithelial staining for alpha-5 (fibronectin receptor sub-unit) was weak in all samples. Alpha-6 (sub-unit of two integrin laminin receptors) showed conspicuous changes in all invasive carcinomas. In normal tissues, there was weak staining of epithelial cytoplasm with alpha-6 antibody and moderate cell membrane staining. Strongest staining was present in a basement membrane distribution. In carcinomas, loss of cytoplasmic and cell membrane staining was variable, but basal membrane staining was diminished or absent in all tumours. Loss of basal membrane staining for alpha-6 integrin corresponded closely to loss of immunoreactivity for its ligand laminin in invasive breast cancer.

Adenofibroma↗

Reduction in apoptosis relative to mitosis in histologically normal epithelium accompanies fibrocystic change and carcinoma of the premenopausal human breast.

The aims of this study in 227 premenopausal women were (a) to determine the mitotic index (MI), the thymidine labelling index (LI), and the apoptotic index (AI) within the epithelial cells of histologically 'normal' human breast biopsy material removed away from the site of either a fibroadenoma or a carcinoma; and (b) to relate differences in the kinetic indices of the 'normal' epithelium to the pathology in the same breast diagnosed as fibroadenoma alone (125 patients), fibroadenoma with accompanying mild fibrocystic change (79 patients), or carcinoma (23 patients). Ratios of the average indices (AI/MI, AI/LI, MI/LI) were also calculated to minimize uncertainties related to the total cell population counted, the denominator in the LI, MI, and AI. All indices and ratios of indices were corrected for age, averaged over the cycle, and expressed as log-transformed values for analysis. Significant (P less than 0.001) reductions in AI and in apoptosis relative to mitosis (reduced AI/MI) were found in 'normal' epithelium from breasts having fibrocystic change (AI = 0.17 +/- 0.02; AI/MI = 1.01 +/- 0.18) and carcinoma (AI = 0.19 +/- 0.04; AI/MI = 0.88 +/- 0.29), compared with breast with fibroadenoma alone (AI = 0.27 +/- 0.03; AI/MI = 1.29 +/- 0.39). In the absence of significant differences in MI and LI between the 'normal' tissue groups, this finding raises the possibility that reduced epithelial cell apoptosis might be causally associated with the development of fibrocystic change and with an increased risk of development of carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenofibroma↗