PATTERNS OF EXPRESSION OF KERATIN 19 AS DETECTED WITH MONOCLONAL ANTIBODIES IN HUMAN BREAST TISSUES AND TUMOURS

The monoclonal antibodies BA 16 and BA 17 directed to different epitopes on human keratin 19 have been tested for their reaction with normal breast and with benign and malignant breast lesions and associated tissue. In Western blots of gel‐separated extracts of fibroadenomas, malignant tumours or normal mammary epithelial cells, the antibodies reacted with only one component of 40 kd molecular weight. Immunoperoxidase staining of sections of normal breast tissues showed all basal cells and a few luminal cells to be unstained by the antibodies. The distribution of the unstained (keratin 19−) luminal cells in the mammary tree is consistent with that of cells with the proliferative potential to give rise to the growth of terminal ductal lobular units (TDLU) seen at pregnancy. A total of 42 benign and 141 malignant lesions were stained with the antibodies, and a clear difference in staining pattern was seen between the benign and malignant tumours. All but 3 of the benign lesions showed a heterogeneous staining pattern with 5–50% unstained cells. In contrast, the cancer cells in 106/116 invasive primary tumours and in all 21 metastatic lesions examined showed a homogeneously positive reaction with antibodies BA16 and BA17: the malignant cells in 4 cases of Paget's disease also showed homogeneously positive staining with the antibody. In the malignant tumours, the observed homogeneity in expression of keratin 19 was confined to the malignant cells; tumour‐associated normal tissue and benign proliferative lesions contained keratin 19−cells. Seven pure in situ tumours were examined and 5 showed the homogeneous pattern of staining characteristic of invasive tumours while 2 contained a high number of keratin 19− cells. A general model is presented to explain the presence of keratin 19− cells in benign proliferation and the dominance of keratin 19− cells in invasive carcinoma.

[1]  E. Lane,et al.  Keratin Antigens in Differentiating Skin , 1985, Annals of the New York Academy of Sciences.

[2]  F. Schuster,et al.  Morphological response of cultured cells to Naegleria amoeba cytopathogenic material. , 1985, Journal of cell science.

[3]  M N Pollak,et al.  Perspectives on clonogenic tumor cells, stem cells, and oncogenes. , 1984, Cancer research.

[4]  M. Lagios,et al.  Pageťs disease of the nipple. Alternative management in cases without or with minimal extent of underlying breast carcinoma , 1984, Cancer.

[5]  H. Smith,et al.  The biology of breast cancer at the cellular level. , 1984, Biochimica et biophysica acta.

[6]  J. Taylor‐Papadimitriou,et al.  Complexity of expression of antigenic determinants, recognized by monoclonal antibodies HMFG-1 and HMFG-2, in normal and malignant human mammary epithelial cells. , 1983, Journal of immunology.

[7]  C. Grund,et al.  Tissue type-specific expression of intermediate filament proteins in a cultured epithelial cell line from bovine mammary gland , 1983, The Journal of cell biology.

[8]  P. Furmanski,et al.  Understanding breast cancer : clinical and laboratory concepts , 1983 .

[9]  C. Griffiths,et al.  The mesothelial keratins: A new family of cytoskeletal proteins identified in cultured mesothelial cells and nonkeratinizing epithelia , 1982, Cell.

[10]  Benjamin Geiger,et al.  The catalog of human cytokeratins: Patterns of expression in normal epithelia, tumors and cultured cells , 1982, Cell.

[11]  T. Sun,et al.  Immunolocalization of keratin polypeptides in human epidermis using monoclonal antibodies , 1982, The Journal of cell biology.

[12]  S. Tseng,et al.  Correlation of specific keratins with different types of epithelial differentiation: Monoclonal antibody studies , 1982, Cell.

[13]  E. Lane Monoclonal antibodies provide specific intramolecular markers for the study of epithelial tonofilament organization , 1982, The Journal of cell biology.

[14]  E. Lane,et al.  Epithelial tonofilaments: investigating their form and function using monoclonal antibodies. , 1982, Cold Spring Harbor symposia on quantitative biology.

[15]  E. Fuchs,et al.  Two distinct classes of keratin genes and their evolutionary significance , 1981, Cell.

[16]  J. Rheinwald,et al.  A new small (40 kd) keratin filament protein made by some cultured human squamous cell carcinomas , 1981, Cell.

[17]  T. Sun,et al.  Intrinsic and extrinsic regulation of the differentiation of skin, corneal and esophageal epithelial cells , 1980, Cell.

[18]  I. Fentiman,et al.  Cholera toxin and analogues of cyclic AMP stimulate the growth of cultured human mammary epithelial cells , 1980, Journal of cellular physiology.

[19]  T. W. Keenan,et al.  Intermediate-sized filaments of the prekeratin type in myoepithelial cells , 1980, The Journal of cell biology.

[20]  L. Lajtha Stem cell concepts. , 1979, Nouvelle revue francaise d'hematologie.

[21]  H. Towbin,et al.  Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[22]  L. Lajtha,et al.  A comparison of cell replacement in bone marrow, testis and three regions of surface epithelium. , 1979, Biochimica et biophysica acta.

[23]  T. Sun,et al.  Keratin cytoskeletons in epithelial cells of internal organs. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[24]  K. Weber,et al.  Antibody to prekeratin. Decoration of tonofilament like arrays in various cells of epithelial character. , 1978, Experimental cell research.

[25]  J. Taylor‐Papadimitriou,et al.  Results on a pilot study of cultures of human lacteal secretions and benign and malignant breast tumors. , 1977, Clinical oncology.

[26]  H M Jensen,et al.  An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. , 1975, Journal of the National Cancer Institute.