Skip to main content
SpringerLink
Log in

Antibodies to intermediate filament proteins in the immunohistochemical identification of human tumours: an overview

  • Papers
  • Published:
The Histochemical Journal Aims and scope Submit manuscript

Summary

Intermediate-sized filament proteins (IFP) are tissue specific in that antibodies to keratin, vimentin, desmin, glial fibrillary acidic protein (GFAP) and the neurofilament proteins can distinguish between cells of epithelial and mesenchymal origin as well as of myogenic and neural origin respectively. Malignant cells retain their tissue-specific IFP, which makes it possible to use these antibodies in tumour diagnosis. Carcinomas are exclusively detected by antibodies to keratin. Monoclonal antibodies to keratin have allowed the differentiation between subgroups of epithelial tumours until now between adenocarcinomas and squamous cell carcinomas. Lymphomas, melanomas and several soft tissue tumours are distinctly recognized by antibodies to vimentin. On the other hand, rhabdomyosarcomas and leiomyosarcomas are positive for desmin, while astrocytomas give a strong reaction with GFAP antibodies. Thus, antibodies to IFP are useful tools for differential diagnosis in surgical pathology.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Altmannsberger, M., Osborn, M., Hölscher, A., Schauer, A. &Weber, K. (1981a) The distribution of keratin type intermediate filaments in human breast cancer. An immunohistological study.Virchows Arch. 37, 277–84.

    Google Scholar 

  • Altmannsberger, M., Osborn, M., Schauer, A. &Weber, K. (1981b) Antibodies to different intermediate filament proteins. Cell type-specific markers on paraffin-embedded human tissues.Lab. Invest. 45, 427–34.

    Google Scholar 

  • Altmannsberger, M., Osborn, M., Trenner, J., Hölscher, A., Weber, K. &Schauer, A. (1982a) Diagnosis of human childhood rhabdomyosarcoma by antibodies to desmin, the structural protein of muscle specific intermediate filaments.Virchows Arch. 39, 203–15.

    Google Scholar 

  • Altmannsberger, M., Weber, K., Hölscher, A., Schauer, A. &Osborn, M. (1982b) Antibodies to intermediate filaments as diagnostic tools. Human gastrointestinal carcinomas express prekeratin.Lab. Invest. 46, 520–6.

    Google Scholar 

  • Anderton, B. H. (1981) Intermediate filaments: a family of homologous structures.J. Musc. Res. Cell Motility 2, 141–66.

    Google Scholar 

  • Asch, B. B., Burnstein, N. A., Vidrich, A. &Sun, T. T. (1981) Identification of mouse mammary epithelial cells by immunofluorescence with rabbit and guinea pig antikeratin antisera.Proc. natn. Acad. Sci., U.S.A.78, 5643–7.

    Google Scholar 

  • Bannasch, P., Zerban, H., Schmid, E. &Franke, W. W. (1980) Liver tumors distinguished by immunofluorescence microscopy with antibodies to proteins of intermediate filaments.Proc. natn. Acad. Sci., U.S.A.77, 4948–52.

    Google Scholar 

  • Bannasch, P., Zerban, H., Schmid, E. &Franke, W. W. (1981) Characterization of cytoskeletal components in epithelial and mesenchymal liver tumors by electron and immunofluorescence microscopy.Virchows Arch. 36, 139–58.

    Google Scholar 

  • Battifora, H., Sun, T. T., Bahu, R. M. &Rao, S. (1980) The use of anti-keratin antiserum as a diagnostic tool: thymoma versus lymphoma.Human Pathol. 11, 635–41.

    Google Scholar 

  • Bejui-Thivolet, F., Viac, J., Thivolet, J. &Faure, M. (1982) Intracellular keratins in normal and pathological bronchial mucosa.Virchows Arch. 395, 87–98.

    Google Scholar 

  • Caselitz, J., Osborn, M., Seifert, G. &Weber, K. (1981) Intermediate filament proteins (prekeratin, vimentin, desmin) in the normal parotid gland and parotid gland tumors.Virchows Arch. 393, 273–86.

    Google Scholar 

  • Dahl, D. &Bignami, A. (1976) Immunogenic properties of the glial fibrillary acidic protein.Brain Res. 116, 150–7.

    Google Scholar 

  • Dahl, D., Rueger, D. C., Bignami, A., Weber, K. &Osborn, M. (1981) Vimentin, the 57 000 molecular weight protein of fibroblasts filaments is the major cytoskeletal component in immature glia.Eur. J. Cell Biol. 24, 191–6.

    Google Scholar 

  • Denk, H., Krepler, R., Lackinger, E.,Artlieb, U. &Franke, W. W. (1982) Biochemical and immunocytochemical analysis of the intermediate filament cytoskeleton in human hepatocellular carcinomas and in hepatic neoplastic nodules of mice.Lab. Invest. 46, 584–96.

    Google Scholar 

  • Fazekas de St. Groth, S. &Scheidegger, D. (1980) Production of monoclonal antibodies: Strategy and tactics.J. Immun. Meth. 35, 1–21.

    Google Scholar 

  • Franke, W. W., Schmid, E., Osborn, M. &Weber, K. (1978) Different intermediate-sized filaments distinguished by immunofluorescence microscopy.Proc. Natn. Acad. Sci., U.S.A.75, 5034–8.

    Google Scholar 

  • Franke, W. W., Appelhans, B., Schmid, E., Freudenstein, C., Osborn, M. &Weber, K. (1979a) Identification and characterization of epithelial cells in mammals by immunofluorescence microscopy using antibodies to prekeratin.Differentiation 15, 7–25.

    Google Scholar 

  • Franke, W. W., Appelhans, B., Schmid, E., Freudenstein, C., Osborn, M. &Weber, K. (1979b). The organization of cytokeratin filaments in the intestinal epithelium.Eur. J. Cell Biol. 19, 255–68.

    Google Scholar 

  • Franke, W. W., Schmid, E., Winter, S., Osborn, M. &Weber, K. (1979c) Widespread occurrence of intermediate-sized filaments of the vimentin type in cultured cells from diverse vertebrates.Expl Cell Res. 132, 25–46.

    Google Scholar 

  • Franke, W. W., Schmid, E., Freudenstein, C., Appelhans, B., Osborn, M., Weber, K. &Keenan, T. W. (1980) Intermediate-sized filaments of the prekeratin type in myoepithelial cells.J. Cell Biol. 84, 633–54.

    Google Scholar 

  • Franke, W. W., Schmid, E., Schiller, D. L., Winter, S., Jarasch, E. D., Moll, R., Denk, H., Jackson, B. W. &Illmensee, K. (1981a) Differentiation related patterns of expression of proteins of intermediate-sized filaments in tissues and cultured cells.Cold Spring Harb. Symp. quant. Biol. 46, 431–53.

    Google Scholar 

  • Franke, W. W., Denk, H., Kalt, R. &Schmid, E. (1981b) Biochemical and immunological identification of cytokeratin proteins present in hepatocytes of mammalian liver tissue.Expl Cell Res. 131, 299–318.

    Google Scholar 

  • Franke, W. W., Mayer, D., Schmid, E., Denk, H. &Borenfreund, E. (1981c) Differences of expression of cytoskeletal proteins in cultured rat hepatocytes and hepatoma cells.Expl Cell Res. 134, 345–65.

    Google Scholar 

  • Gabbiani, G., Kapanci, Y., Barazzone, P. &Franke, W. W. (1981) Immunochemical identification of intermediate-sized filaments in human neoplastic cells. A diagnostic aid for the surgical pathologists.Am. J. Pathol. 104, 206–16.

    Google Scholar 

  • Geisler, N. &Weber, K. (1980) Purification of smooth-muscle desmin and a protein-chemical comparison of desmins from chicken gizzard and hog stomach.Eur. J. Biochem. 111, 425–33.

    Google Scholar 

  • Gusterson, B., Mitchell, D., Warburton, M. &Sloane, J. (1982) Immunohistochemical localization of keratin in human lung tumours.Virchows Arch. 394, 269–77.

    Google Scholar 

  • Herman, C. J., Moesker, O., Kant, A. Vooijs, G. P. &Ramaekers, F. C. S. (1983) Grawitz tumor is a carcinosarcomaLab. Invest. 48, 35A-6A.

    Google Scholar 

  • Holtzer, H., Bennet, G. S., Tapscott, S. J., Croop, J. M. &Toyama, Y. (1981) Intermediate-size filaments: Changes in syntheses and distribution in cells of the myogenic and neurogenic lineages.Cold Spring Harb. Symp. quant. Biol. 46, 317–29.

    Google Scholar 

  • Jackson, B. W., Grund, C., Schmid, E., Bürkí, K., Franke, W. W. &Toyama, Y. (1981) Formation of cytoskeletal elements during mouse embryogenesis: I. Intermediate filaments of the cytokeratin type and desmosomes in preimplantation embryos.Differentiation 17, 161–79.

    Google Scholar 

  • Jackson, B. W., Grund, C., Winters, S., Franke, W. W. &Illmensee, K. (1981) Formation of cytoskeletal elements during mouse embryogenesis: II. Epithelial differentiation and intermediate-sized filaments in early post-implantation embryos.Differentiation 20, 203–16.

    Google Scholar 

  • Jessen, K. R. &Mirsky, R. (1980) Glial cells in the enteric nervous system contain glial fibrillary acidic protein.Nature, Lond. 286, 736–7.

    Google Scholar 

  • Jörgensen, A. O., Subrahmanyan, L., Turnbull, C. &Kalnins, V. I. (1976) Localization of the neurofilament protein in neuroblastoma cells by immunofluorescent staining.Proc. natn. Acad. Sci., U.S.A.73, 3192–6.

    Google Scholar 

  • Klymkowsky, M. W. (1982) Vimentin and keratin intermediate filament systems in cultured PtK2 epithelial cells are interrelated.EMBO J. 1, 161–5.

    Google Scholar 

  • Köhler, G. &Milstein, C. (1975) Continuous cultures of fused cells secreting antibody of predefined specificity.Nature, Lond. 256, 495–7.

    Google Scholar 

  • Krepler, R., Denk, H., Weirich, E., Schmid, E. &Franke, W. W. (1981) Keratin-like proteins in normal and neoplastic cells of human and rat mammary gland as revealed by immunofluorescence microscopy.Differentiation 20, 242–52.

    Google Scholar 

  • Krepler, R., Denk, H., Artlieb, U. &Moll, R. (1982) Immunocytochemistry of intermediate filament proteins present in pleomorphic adenomas of the human parotid gland: characterization of different cell types in the same tumor.Differentiation 21, 191–9.

    Google Scholar 

  • Lane, E. B. (1982) Monoclonal antibodies provide specific intramolecular markers for the study of epithelial tonofilament organization.J. Cell Biol. 92, 665–73.

    Google Scholar 

  • Lazarides, E. (1980) Intermediate filaments as mechanical integrators of cellular space.Nature, Lond. 283, 249–56.

    Google Scholar 

  • Lazarides, E. (1981) Intermediate filaments-Chemical heterogeneity in differentiation.Cell. 23, 649–50.

    Google Scholar 

  • Lazarides, E. (1982) Intermediate filaments: a chemically heterogeneous developmentally regulated class of proteins.Ann. Rev. Biochem. 51, 219–50.

    Google Scholar 

  • Lehto, V. P., Stenman, S., Miettinen, M., Dahl, D. &Virtanen, I. (1983) Expression of neural-type of intermediate filaments as a distinguishing feature between oat cell carcinoma and other lung cancers.Am. J. Pathol. 110, 113–8.

    Google Scholar 

  • Löning, T., Staquet, M. J., Thivolet, J. &Seifert, G. (1980) Keratin polypeptides distribution in normal and diseased human epidermis and oral mucosa. Immunohistochemical study on unaltered epithelium and inflammatory, premalignant and malignant lesions.Virchows Arch. A. 388, 273–88.

    Google Scholar 

  • Madri, J. A. &Barwick, K. W. (1982) An immunohistochemical study of nasopharyngeal neoplasms using keratin antibodies. Epithelial versus nonepithelial neoplasms.Am. J. Surg. Pathol. 6, 143–9.

    Google Scholar 

  • Miettinen, M., Lehto, V. P., Badley, R. A. &Virtanen, I. (1982a) Alveolar rhabdomyosarcoma — demonstration of the muscle type of intermediate filament protein, desmin, as a diagnostic aid.Am. J. Pathol. 108, 246–51.

    Google Scholar 

  • Miettinen, M., Lehto, V. P., Vartio, T. &Virtanen, I. (1982b) Epitheloid sarcoma. Ultrastructural and immunohistological features suggesting a synovial origin.Archs. Pathol. Lab. Med. 106, 620–3.

    Google Scholar 

  • Miettinen, M., Lehto, V. P. &Virtanen, I. (1982c) Keratin positivity in the epithelial-like cells in classical biphasic synovial sarcoma.Virchows Arch. 40, 157–61.

    Google Scholar 

  • Miettinen, M., Lehto, V. P., Badley, R. A. &Virtanen, I. (1982d) Expression of intermediate filaments in soft tissue sarcomas.Int. J. Cancer. 30, 541–6.

    Google Scholar 

  • Osborn, M., Franke, W. W. &Weber, K. (1977) Visualisation of a system of filaments 7–10 nm thick in cultured cells of an epitheloid line (Pt K2) by immunofluorescence microscopy.Proc. natn. Acad. Sci., U.S.A.74, 2490–4.

    Google Scholar 

  • Osborn, M., Geisler, N., Shaw, G., Sharp, G. &Weber, K. (1981) Intermediate filaments.Cold Spring Harb. Symp. quant. Biol. 46, 2490–4.

    Google Scholar 

  • Osborn, M., Altmannsberger, M., Shaw, G., Schauer, A. &Weber, K. (1982) Various sympathetic derived human tumors differ in neurofilament expression.Virchows Arch. 40, 141–56.

    Google Scholar 

  • Ramaekers, F. C. S., Dunia, I., Dodemont, H. J., Benedetti, E. L. &Bloemendal, H. (1982c) Lenticular intermediate-sized filaments: biosynthesis and interaction with the plasma membrane.Proc. natn. Acad. Sci.,U.S.A.79, 3208–12.

    Google Scholar 

  • Ramaekers, F. C. S., Haag, D., Kant, A., Moesker, O., Jap, P. H. K. & Vooijs, G. P. (1983c) Coexpression of keratin- and vimentin-type intermediate filaments in human metastatic carcinoma cells.Proc. natn. Acad. Sci., U.S.A. (in press).

  • Ramaekers, F. C. S., Osborn, M., Schmid, E., Weber, K., Bloemendal, H. &Franke, W. W. (1980) Identification of the cytoskeletal proteins in lens-forming cells, a special epithelioid cell type.Expl Cell Res. 127, 309–27.

    Google Scholar 

  • Ramaekers, F. C. S., Puts, J. J. G., Kant, A., Moesker, O., Jap, P. H. K. &Vooijs, G. P. (1981) Use of antibodies to intermediate filaments in the characterization of human tumors.Cold Spring Harb. Symp. quant. Biol. 46, 331–9.

    Google Scholar 

  • Ramaekers, F. C. S., Puts, J. J. G., Kant, A., Moesker, O., Jap, P. H. K. &Vooijs, G. P. (1982a) Antibodies to intermediate filaments as a tool in tumordiagnosis.Cell Biol. Int. Rep. 6, 625.

    Google Scholar 

  • Ramaekers, F. C. S., Puts, J. J. G., Kant, A., Moesker, O., Jap, P. H. K. &Vooijs, G. P. (1982b) Differential diagnosis of human carcinomas, sarcomas and their metastases using antibodies to intermediate-sized filaments.Eur. J. Cancer Clin. Oncol. 18, 1251–7.

    Google Scholar 

  • Ramaekers, F. C. S., Puts, J. J. G., Moesker, O., Kant, A., Jap, P. H. K. & Vooijs, G. P. (1983a) Demonstration of keratin in human adenocarcinomas (in press).

  • Ramaekers, F. C. S., Puts, J. J. G., Moesker, O., Kant, A., Vooijs, G. P. &Jap, P. H. K. (1983b) Intermediate filaments in malignant melanomas. Identification and use as a marker in surgical pathology.J. clin Inv. 71, 635–43.

    Google Scholar 

  • Ramaekers, F. C. S., Verheijen, R. H. M., Moesker, O., Kant, A., Vooijs, G. P. & Herman, C. J. (1983d) Mesodermal mixed tumor: Diagnosis by analysis of intermediate filament proteins.Am. J. Surg. Pathol. (in press).

  • Schlegel, R., Banks-Schlegel, S., McLeod, J. A. &Pinkus, G. S. (1980a) Immunoperoxidase localization of keratin in human neoplasms, a preliminary survey.Am. J. Pathol. 101, 635–41.

    Google Scholar 

  • Schlegel, R., Banks-Schlegel, S. &Pinkus, G. S. (1980b) Immunohistochemical localization of keratin in normal human tissues.Lab. Invest. 42, 91–6.

    Google Scholar 

  • Schliwa, M. &Van Blerkom, J. (1981) Structural interaction of cytoskeletal components.J. Cell Biol. 90, 222–35.

    Google Scholar 

  • Schnitzer, J., Franke, W. W. &Schachner, M. (1981) Immunocytochemical demonstration of vimentin in astrocytes and ependymal cells of developing and adult mouse nervous system.J. Cell Biol. 90, 435–47.

    Google Scholar 

  • Shaw, G., Osborn, M. &Weber, K. (1981) An immunofluorescence microscopical study of the neurofilament triplet proteins, vimentin and glial fibrillary acidic protein within the adult rat brain.Lur. J. Cell Biol. 26, 68–82.

    Google Scholar 

  • Sieinski, W., Dorsett, B. &Ioachim, H. L. (1981) Identification of prekeratin by immunofluorescence staining in the differential diagnosis of tumors.Human Pathol. 12, 452–8.

    Google Scholar 

  • Summerhayes, I. C., Chang, Y. S. E., Sun, T. T. &Chen, L. B. (1981) Expression of keratin and vimentin in rabbit bladder epithelial cells at different stages of benzo(a)pyrene-induced neoplastic progression.J. Cell Biol. 90, 63–9

    Google Scholar 

  • Sun, T. T., Shih, C. &Green, H. (1979) Keratin cytoskeletons in epithelial cells of internal organs.Proc. natn. Acad. Sci. U.S.A. 76, 2813–7.

    Google Scholar 

  • Tascos, N. A., Parr, J. &Gonatas, N. K. (1982) Immunocytochemical study of the glial fibrillary acidic protein in human neoplasms of the central nervous system.Human Pathol. 13, 454–8.

    Google Scholar 

  • Warhol, M. J., Hickey, W. F. &Corson, J. M. (1982) Malignant mesothelioma. Ultrastructural distinction from adenocarcinoma.Am. J. Surg. Pathol. 6, 307–14.

    Google Scholar 

  • Yen, S. H. &Fields, K. L. (1981) Antibodies to neurofilament, glial filament and fibroblast intermediate filament proteins bind to different cell types of the nervous system.J. Cell Biol. 88, 115–26.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, University of Nijmegen, Nijmegen, The Netherlands

    F. C. S. Ramaekers, J. J. G. Puts, O. Moesker, A. Kant, A. Huysmans, D. Haag, C. J. Herman & G. P. Vooijs

  2. Department of Cytology and Histology, University of Nijmegen, Nijmegen, The Netherlands

    P. H. K. Jap

Authors
  1. F. C. S. Ramaekers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. J. G. Puts
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. Moesker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Kant
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Huysmans
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. D. Haag
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P. H. K. Jap
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. C. J. Herman
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G. P. Vooijs
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ramaekers, F.C.S., Puts, J.J.G., Moesker, O. et al. Antibodies to intermediate filament proteins in the immunohistochemical identification of human tumours: an overview. Histochem J 15, 691–713 (1983). https://doi.org/10.1007/BF01002988

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01002988

Keywords

Search

Navigation