Skip to main content
Log in

Epidermal growth factor receptor expression and growth fraction in human tumours of the nervous system

  • Published:
Virchows Archiv A Aims and scope Submit manuscript

Summary

100 tumours of the human nervous system were investigated by means of immunohistochemistry in order to determine the expression of epidermal growth factor receptor (EGFr) and the proliferative activity as evaluated by demonstration of the proliferation-associated Ki-67 antigen. Epidermal growth factor receptor immunoreactivity was present in 79% (23/29) of the high-grade malignant gliomas examined but in only 9% (2/22) of the low-grade gliomas. Besides the gliomas, EGFr-expression was detectable in smaller amounts in most (13/15) meningiomas, in one anaplastic neurinoma and in individual tumour cells of one medulloblastoma. In addition, EGFr-expression was found in 50% (6/12) of metastatic carcinomas. Seven of eight medulloblastomas, two cerebral primitive neuroectodermal tumours (PNETs), three benign neurinomas, one ganglioneuroma, one metastatic intracerebral malignant melanoma, three spinal plasmocytomas and one immunocytoma showed no detectable EGFr-expression. Our results indicate that (1) the expression of EGFr in human tumours of the nervous system depends on the histological tumour type and (2) in the glioma group is related to the grade of malignancy. A close correlation between EGFrexpression and proliferative activity as evaluated by Ki-67 staining could not, however, be established.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Adamson ED, Rees AR (1981) Epidermal growth factor receptors. Mol Cell Biochem 34:129–152

    Google Scholar 

  • Bell C, Harsh G, Rosenblum M, Meltzer P, Trent J (1986) Numeric and structural alterations of chromosome 7 in human brain tumors: correlation with expression of epidermal growth factor receptor (EGFR). Proc Annu Meet Am Assoc Cancer Res 27:37 (abstract)

    Google Scholar 

  • Berger MS, Greenfield C, Gullick WJ, Haley J, Downward J, Neal DE, Harris AL, Waterfield MD (1987a) Evaluation of epidermal growth factor receptors in bladder tumours. Br J Cancer 56:533–537

    Google Scholar 

  • Berger MS, Gullick WJ, Greenfield C, Evans S, Addis BJ, Waterfield MD (1987b) Epidermal growth factor receptors in lung tumors. J Pathol 152:297–307

    Google Scholar 

  • Bravo R, Burckhardt J, Curran T, Müller R (1985) Stimulation and inhibition of growth by EGF in different A431 cell clones is accompanied by the rapid induction of c-fos and c-myc proto-oncogenes. EMBO J 4:1193–1197

    Google Scholar 

  • Carpenter G (1985) Epidermal growth factor: Biology and receptor metabolism. J Cell Sci Suppl 3:1–9

    Google Scholar 

  • Carpenter G, Cohen S (1975) Human epidermal growth factor and the proliferation of human fibroblasts. J Cell Physiol 88:227–238

    Google Scholar 

  • Cohen S (1962) Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eylid opening in the newborn animal. J Biol Chem 247:7609–7611

    Google Scholar 

  • Collins VP, James CD, Carlbom E, Dumanski JP, Hansen MF, Nordenskjöld M, Cavenee WK (1988) The evolution of malignant astrocytomas:stage specific genomic alterations. Arch Suisses Neurol Psychiat 139:78 (abstract)

    Google Scholar 

  • Damjanov I, Mildner B, Knowles BB (1986) Immunohistochemical localization of the epidermal growth factor receptor in normal human tissues. Lab Invest 55:588–592

    Google Scholar 

  • Deckert M, Reifenberger G, Wechsler W (1988) Determination of the proliferative potential of human brain tumors using the monoclonal antibody Ki-67. J Cancer Res Clin Oncol (in press)

  • Downward J, Yarden Y, Mayes E, Scrace G, Totty N, Stockwell P, Ullrich A (1984) Close similarity of EGF receptor and v-erb-B-oncogene protein sequences. Nature 307:521–527

    Google Scholar 

  • Eisbruch A, Blick M, Lee JS, Sacks PG, Guttermann J (1987) Analysis of the epidermal growth factor receptor gene in fresh human head and neck tumors. Cancer Res 47:3603–3605

    Google Scholar 

  • Epenetos AA, Courtenay-Luck N, Pickering D, Hooker G, Durbin H, Lavender JP, McKenzie CG (1985) Antibody guided irradiation of brain glioma by arterial infusion of radioactive monoclonal antibody against epidermal growth factor receptor and blood group A antigen. Br Med J 290:1463–1466

    Google Scholar 

  • Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715

    Google Scholar 

  • Gerdes J, Schwab U, Lemke H, Stein H (1983) Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31:13–20

    Google Scholar 

  • Green MR, Basketter DA, Couchman JR, Rees DA (1983) Distribution and number of EGF receptors in skin is related to epithelial cell growth. Devel Biol 100:506–512

    Google Scholar 

  • Gullick WJ, Julian D, Downward H, Marsden JJ, Waterfield MD (1984) A radioimmunoassay for human epidermal growth factor receptor. Anal Biochem 141:253–261

    Google Scholar 

  • Gullick WJ, Berger MS, Bennett PLP, Rothbard JB, Waterfield D (1986) Expression of epidermal growth factor receptors on human cervical, ovarian, and vulval carcinomas. Cancer Res 46:285–292

    Google Scholar 

  • Gusterson B, Cowley G, Smith JA, Ozanne B (1984) Cellular localization of human EGF receptors. Cell Biol Int Rep 8:649–658

    Google Scholar 

  • Haeder M, Rotsch M, Bepler G, Hennig C, Havemann K, Heimann B, Moelling K (1988) Epidermal growth factor receptor expression in human lung cancer cell lines. Cancer Res 48:1132–1136

    Google Scholar 

  • Heldin CH, Betsholtz C, Claesson-Welsh L, Westermark B (1987) Subversion of growth regulatory pathways in malignant transformation. Biochimica et Biophysica Acta 907:219–244

    Google Scholar 

  • Henn W, Blin N, Zang KD (1986) Polysomy of chromosome 7 is correlated with overexpression of the erbB oncogene in human glioblastoma cell lines. Hum Genet 74:104–106

    Google Scholar 

  • Hunter T (1984) The epidermal growth factor receptor gene and its product. Nature 311:414–416

    Google Scholar 

  • Hsu SM, Raine L, Fanger H (1981) The use of anti-avidin anti-body and avidin-biotin-peroxidase-complex in immunoperoxidase techniques. Am J Clin Pathol 75:816–821

    Google Scholar 

  • Kleihues P, Kiessling M, Janzer RC (1987) Morphological markers in neuro-oncology. In: Seifert G (ed) Current Topics in Pathology, Vol 77. Morphological tumor markers. Springer, Berlin Heidelberg New York, pp 307–338

    Google Scholar 

  • Libermann TA, Razon N, Bartal AD, Yarden Y, Schlessinger J, Soreq H (1984) Expression of epidermal growth factor receptors in human brain tumors. Cancer Res 44:753–760

    Google Scholar 

  • Libermann TA, Nusbaum HR, Razon N, Kris R, Lax I, Soreq H, Whittle N, Waterfield MD, Ullrich A, Schlessinger J (1985) Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 313:144–147

    Google Scholar 

  • Malden LT, Novak U, Kaye AH, Burgess AW (1988) Selective amplification of the cytoplasmic domain of the epidermal growth factor receptor gene in glioblastoma multiforme. Cancer Res 48:2711–2714

    Google Scholar 

  • Massague J (1983) EGF-like TGF. J Biol Chem 258:13614–13620

    Google Scholar 

  • Müller R, Bravo R, Burckhardt J, Curran T (1984) Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature 312:716–720

    Google Scholar 

  • Nilsen-Hamilton M, Holley RW (1983) Rapid selective effects by a growth inhibitor and EGF on the incorporation of35S-methionine into proteins secreted by African green monkey (BSC-1) cells. Proc Natl Acad Sci USA 80:5636–5640

    Google Scholar 

  • Nister M, Libermann TA, Betsholtz C, Pettersson M, Claesson-Welsh L, Heldin CH, Schlessinger J, Westermark B (1988) Expression of messenger RNAs for platelet-derived growth factor and transforming growth factor alpha and their receptors in human malignant glioma cell lines. Cancer Res 48:3910–3918

    Google Scholar 

  • Pantazis P, Pelicci PG, Dalla-Favera R, Antoniades HN (1985) Synthesis and secretion of proteins resembling platelet-derived growth factor by human glioblastoma und fibrosarcoma cells in culture. Proc Natl Acad Sci USA 82:2404–2408

    Google Scholar 

  • Perentes E, Rubinstein LJ (1987) Recent applications of immuno-peroxidase histochemistry in human neuro-oncology. An update. Arch Pathol Lab Med 111:796–812

    Google Scholar 

  • Pike LJ, Marquardt H, Todaro G, Gallis B, Casnellie JE, Bornstein P, Krebs EG (1982) TGF and EGF stimulate the phosphorylation of a synthetic, tyrosine-containing peptide in a similar manner. J Biol Chem 257:14628–14631

    Google Scholar 

  • Reifenberger G, Szymas J, Wechsler W (1987) Differential expression of glial- and neuronal-associated antigens in human tumors of the central and peripheral nervous system. Acta Neuropathol (Berl) 74:105–123

    Google Scholar 

  • Sainsbury JRC, Malcolm AJ, Appleton DR, Farndon JR, Harris AL (1985) Presence of epidermal growth factor receptor as an indicator of poor prognosis in patients with breast cancer. J Clin Pathol 38:1225–1228

    Google Scholar 

  • Samuels V, Pantazis CG, Allen MB, Wright S, Yaghmai F, Lobel S (1987) Immunohistochemical detection of transforming growth factor alpha in tumors of glial origin. Proc Annu Meet Am Assoc Cancer Res 28:55 (abstract)

    Google Scholar 

  • Schlessinger J, Geiger B (1981) EGF induces redistribution of actin and alpha-actinin in human epidermal carcinoma cells. Exp Cell Res 134:273–279

    Google Scholar 

  • Steck PA, Yung WK (1987) Identification and characterization of an altered epidermal growth factor receptor in human glioma cells. Proc Annu Meet Am Assoc Cancer Res 28:60 (abstract)

    Google Scholar 

  • Stroobant P, Rice AP, Gullick WJ, Cheng DJ, Kerr IM, Waterfield MD (1985) Purification and characterisation of vaccinia virus growth factor. Cell 42:383–393

    Google Scholar 

  • Stromberg K, Hudgins WR, Dormon LS, Henderson LE, Sowder RC, Sherrell BJ, Mount CD, Orth DN (1987) Human brain tumor-associated urinary high molecular weight transforming growth factor: a high molecular weight form of epidermal growth factor. Cancer Res 47:1190–1196

    Google Scholar 

  • Ushiro H, Cohen S (1980) Identification of phosphotyrosine as a product of epidermal growth factor activated protein kinase in A 431 cell membranes. J Biol Chem 255:8263

    Google Scholar 

  • Takahashi H, Herlyn D, Atkinson B, Powe J, Rodeck U, Alavi A, Bruce DA, Koprowski H (1987) Radioimmunodetection of human glioma xenografts by monoclonal antibody to epidermal growth factor receptor. Cancer Res 47:3847–3850

    Google Scholar 

  • Veale D, Ashcroft T, Marsh C, Gibson GJ, Harris AL (1987) Epidermal growth factor receptors in non-small cell lung cancer. Br J Cancer 55:513–516

    Google Scholar 

  • Velu TJ, Beguinot L, Vass WC, Willingham MC, Merlino GT, Pastan I, Lowy DR (1987) Epidermal growth factor-dependent transformation by a human EGF receptor proto-oncogen. Science 238:1408–1410

    Google Scholar 

  • Waterfield MD, Mayes ELY, Stroobant P, Bennett PLP, Young S, Goodfellow AN, Banting GS, Ozanne B (1982) A monoclonal antibody to the human EGF receptor. J Cell Biochem 20:149–161

    Google Scholar 

  • Weisman AS, Raguet SS, Kelly PA (1987) Characterization of the epidermal growth factor receptor in human meningioma. Cancer Res 47:2172–2176

    Google Scholar 

  • Westermark B (1976) Density dipendent proliferation of human glia cells stimulated by epidermal growth factor. Biochem Biophys Res Com 69:304–310

    Google Scholar 

  • Westphal M, Herrmann HD (1986) Epidermal growth factorreceptors on cultured human meningioma cells. Acta Neurochir (Wien) 83:62–66

    Google Scholar 

  • Wong AJ, Bigner SH, Bigner DD, Kinzler KW, Hamilton SR, Vogelstein B (1987) Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc Natl Acad Sci 84:6899–6903

    Google Scholar 

  • Wrba F, Reiner A, Ritzinger E, Holzner JH (1988) Expression of epidermal growth factor receptors on breast carcinomas in relation to growth fractions, oestrogen receptor status and morphological criteria. Path Res Pract 183:25–29

    Google Scholar 

  • Yasui W, Hata J, Yokozaki H, Nakatani H, Ochiai A, Ito H, Tahara E (1988) Interaction between epidermal growth factor and its receptor in progression of human gastric carcinoma. Int J Cancer 41:211–217 (1988)

    Google Scholar 

  • Zülch KJ (1979) Histological typing of tumours of the central nervous system. International Histological Classification of Tumours. WHO Geneva

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by: Deutsche Forschungsgemeinschaft, SFB 200

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reifenberger, G., Prior, R., Deckert, M. et al. Epidermal growth factor receptor expression and growth fraction in human tumours of the nervous system. Vichows Archiv A Pathol Anat 414, 147–155 (1989). https://doi.org/10.1007/BF00718594

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00718594

Key words

Navigation