Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Frequent expression of 75 kDa nerve growth factor receptor and phosphotyrosine in human peripheral nerve tumours: an immunohistochemical study on paraffin-embedded tissues

  • 37 Accesses

  • 13 Citations


One hundred and three benign, and 10 malignant peripheral nerve tumours were examined immunohistochemically for expression of 75 kDa nerve growth factor receptor (NGFR). In benign tumours NGFR was demonstrated at 61% in neurinoma, 71% in neurofibroma, 93% in neurofibromatosis and 90% in traumatic neuroma. Malignant neurogenic tumours were 100% positive for NGFR. Phosphotyrosine-immunoreactivity was detected in 76% of NGFR-positive tumours but the frequency of immunostained tumour cells was low. These results suggest that both benign and malignant peripheral nerve tumours express 75 kDa NGFR. The receptor seems to serve as growth signal transduction of the tumour cells in terms of phosphorylation of the tyrosine residue of the receptor or the target protein of the NGFR protein tyrosine kinase.

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


  1. 1.

    Borrello MG, Bongarzone I, Pierotti MA, Luksch R, Gasparini M, Collini P, Pilotti S, Rizzetti MG, Mondellini P, De Bernardi B, DiMartino D, Garaventa A, Brisigotti M, Tonini GP (1993) trk and ret proto-oncogene expression in human neuroblastoma specimens: high frequency of trk expression in non-advanced stages. Int J Cancer 54: 540–545

  2. 2.

    Brodeur GM (1993) TRK-A expression in neuroblastomas: a new prognostic marker with biological and clinical significance. J Natl Cancer Inst 85: 344–345

  3. 3.

    Chernoff J, Schievella AR, Jost CA, Erikson RL, Neel BG (1990) Cloning of a cDNA for a major human protein-tyrosine-phosphatase. Proc Natl Acad Sci USA 87: 2735–2739

  4. 4.

    Chesa PG, Rettig WJ, Thomson TM, Old LJ, Malamed MR (1988) Immunohistochemical analysis of nerve growth factor receptor expression in normal and malignant human tissues. J Histochem Cytochem 36: 383–389

  5. 5.

    Cool DE, Tonks NK, Charbonneau H, Walsh KA, Fischer EH, Krebs EG (1989) cDNA isolated from a human T-cell library encodes a member of the protein-tyrosine-phosphatase family. Proc Natl Acad Sci USA 86: 5257–5261

  6. 6.

    Enzinger FM, Lattes R, Torloni R (1969) Histological typing of soft tissue tumours. International histological classification of tumours. No. 3, World Health Organization, Geneva

  7. 7.

    Godfrey EW, Shooter EM (1986) Nerve growth factor receptors on chick embryo sympathetic ganglion cells: binding characteristics and development. J Neurosci 6: 2543–2550

  8. 8.

    Green LA, Tischler AS (1976) Establishment of a noradrenergic clonal line of a rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci USA 73: 2424–2428

  9. 9.

    Gu M, York JD, Warshawsky I, Majerus PW (1991) Identification, cloning and expression of a cytosolic megakaryocyte protein-tyrosine-phosphatase with sequence homology to cytoskeletal protein 4.1. Proc Natl Acad Sci USA 88: 5867–5871

  10. 10.

    Hempstead BL, Martin-Zanca D, Kapland DR, Parada LF, Chao MV (1991) High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor. Nature 350: 678–683

  11. 11.

    Hunter T (1989) Protein-tyrosine phosphatases: the other side of the coin. Cell 56: 1013–1016

  12. 12.

    Kaplan DR, Martin-Zanca D, Parada LF (1991a) Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF. Nature 350: 158–160

  13. 13.

    Kaplan DR, Hempstead BL, Martin-Zanca D, Chao MV, Parada LF (1991b) The trk proto-oncogene product: a signal transducing receptor for nerve growth factor. Science 252: 554–558

  14. 14.

    Klein R, Jing S, Nanduri V, O'Rourke E, Barbacid M (1991) trk proto-oncogene encodes a receptor for nerve growth factor. Cell 65: 189–197

  15. 15.

    Krueger NX, Streuli M, Saito H (1990) Structural diversity and evolution of human receptor-like protein tyrosine phosphatase. EMBO J 9: 3241–3252

  16. 16.

    Lombroso PJ, Murdoch G, Lerner M (1991) Molecular characterization of a protein-tyrosine-phosphatase enriched in striatum. Proc Natl Acad Sci USA 88: 7242–7246

  17. 17.

    MacGrogan D, Saint-André J-P, Dicou E (1992) Expression of nerve growth factor and nerve growth factor receptor genes in human tissues and in prostatic adenocarcinoma cell lines. J Neurosci 59: 1381–1391

  18. 18.

    Meakin SO, Suter U, Drinkwater CC, Welcher AA, Shooter EM (1992) The rat trk protooncogene product exhibits properties characteristic of the slow nerve growth factor receptor. Proc Natl Acad Sci USA 89: 2374–2378

  19. 19.

    Nakagawara A, Arima M, Azar CG, Scavarda NJ, Brodeur GM (1992) Inverse relationship between trk expression and N-myc amplification in human neuroblastomas. Cancer Res 52: 1364–1368

  20. 20.

    Ohmichi M, Decker SJ, Saltiel AR (1991) Nerve growth factor induces the association of a 130-kD phosphoprotein with its receptor in PC-12 pheochromocytoma cells. Cell Reg 2: 691–697

  21. 21.

    Perosio PM, Brooks JJ (1988) Expression of nerve growth factor receptor in paraffin-embedded soft tissue tumors. Am J Pathol 132: 152–160

  22. 22.

    Ragsdale C, Woodgett J (1991) trking neurotrophic receptors. Nature 350: 660–661

  23. 23.

    Ross AH, Grob P, Bothwell M, Elder DE, Ernst CS, Marano N, Ghrist BFD, Slemp CC, Herlyn M, Atkinson B, Koprowski H (1984) Characterization of nerve growth factor receptor in neural crest tumors using monoclonal antibodies. Proc Natl Acad Sci USA 81: 6681–6685

  24. 24.

    Ross AH (1991) Identificatin of tyrosine kinase trk as a nerve growth factor receptor. Cell Reg 2: 685–690

  25. 25.

    Schechter AL, Bothwell MA (1981) Nerve growth factor receptors on PC12 cells: evidence for two receptor classes with differing cytoskeletal association. Cell 24: 867–874

  26. 26.

    Sternberger LA (1986) Immunohistochemistry 3rd edn, John Wiley, New York, p100

  27. 27.

    Sutter A, Riopelle RJ, Harris-Warrick RM, Shooter EM (1979) Nerve growth factor receptors. Characterization of two distinct classes of binding sites on chick embryo sensory ganglia cells. J Biol Chem 254: 5972–5982

  28. 28.

    Suzuki T, Ajioka Y, Kogure S (1988) Monoclonal S-100 immunocytochemistry of pigmented naevi with tactile-like corpuscles. J Pathol 155: 121–126

  29. 29.

    Thomson TM, Rettig WJ, Chesa GP, Green SH, Carrato Mena CA, Old LJ (1988) Expression of human nerve growth factor receptors on cells derived from all three germ layers. Exp Cell Res 174: 533–539

  30. 30.

    Yang Q, Tonks NK (1991) Isolation of cDNA clone encoding a human protein-tyrosine phosphatase with homology to the cytoskeletal-associated proteins band 4.1, ezrin, and tralin. Proc Natl Acad Sci USA 88: 5949–5953

Download references

Author information

Correspondence to T. Suzuki.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hoshi, N., Hiraki, H., Yamaki, T. et al. Frequent expression of 75 kDa nerve growth factor receptor and phosphotyrosine in human peripheral nerve tumours: an immunohistochemical study on paraffin-embedded tissues. Vichows Archiv A Pathol Anat 424, 563–568 (1994). https://doi.org/10.1007/BF00191444

Download citation

Key words

  • Nerve growth factor receptor Phosphotyrosine
  • Peripheral nerve tumours Immunohistochemistry