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.
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Adamson ED, Rees AR (1981) Epidermal growth factor receptors. Mol Cell Biochem 34:129–152
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)
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
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
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
Carpenter G (1985) Epidermal growth factor: Biology and receptor metabolism. J Cell Sci Suppl 3:1–9
Carpenter G, Cohen S (1975) Human epidermal growth factor and the proliferation of human fibroblasts. J Cell Physiol 88:227–238
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
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)
Damjanov I, Mildner B, Knowles BB (1986) Immunohistochemical localization of the epidermal growth factor receptor in normal human tissues. Lab Invest 55:588–592
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
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
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
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
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
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
Gullick WJ, Julian D, Downward H, Marsden JJ, Waterfield MD (1984) A radioimmunoassay for human epidermal growth factor receptor. Anal Biochem 141:253–261
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
Gusterson B, Cowley G, Smith JA, Ozanne B (1984) Cellular localization of human EGF receptors. Cell Biol Int Rep 8:649–658
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
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
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
Hunter T (1984) The epidermal growth factor receptor gene and its product. Nature 311:414–416
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
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
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
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
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
Massague J (1983) EGF-like TGF. J Biol Chem 258:13614–13620
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
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
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
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
Perentes E, Rubinstein LJ (1987) Recent applications of immuno-peroxidase histochemistry in human neuro-oncology. An update. Arch Pathol Lab Med 111:796–812
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
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
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
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)
Schlessinger J, Geiger B (1981) EGF induces redistribution of actin and alpha-actinin in human epidermal carcinoma cells. Exp Cell Res 134:273–279
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)
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
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
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
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
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
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
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
Weisman AS, Raguet SS, Kelly PA (1987) Characterization of the epidermal growth factor receptor in human meningioma. Cancer Res 47:2172–2176
Westermark B (1976) Density dipendent proliferation of human glia cells stimulated by epidermal growth factor. Biochem Biophys Res Com 69:304–310
Westphal M, Herrmann HD (1986) Epidermal growth factorreceptors on cultured human meningioma cells. Acta Neurochir (Wien) 83:62–66
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
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
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)
Zülch KJ (1979) Histological typing of tumours of the central nervous system. International Histological Classification of Tumours. WHO Geneva
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Supported by: Deutsche Forschungsgemeinschaft, SFB 200
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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
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DOI: https://doi.org/10.1007/BF00718594